diff --git a/examples/demo.html b/examples/demo.html
index e0703e9..7c0de6c 100644
--- a/examples/demo.html
+++ b/examples/demo.html
@@ -42,8 +42,8 @@
 <script src="https://cdn.jsdelivr.net/npm/bootstrap@4.5.2/dist/js/bootstrap.min.js"></script>
 <script src="https://cdn.jsdelivr.net/npm/datatables@1.10.17/media/js/jquery.dataTables.min.js"></script>
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Ionic glutamate acceptor 2 (GluA2) is involved in many important physiological and pathological processes in the brain. GluA2 is tetrameric (dimer of dimer), and its ligand binding domain (LBD) dimer plays a key role in the ligand gating of GluA2. As the LBD only weakly dimerizes by itself, there has been few studies on the ensemble structure of LBD dimer. We found that the LBD dimer adopts an array of relative orientations as the GluA2 shifts into the desensitized state. We thus propose to determine the ensemble structure of LBD dimer. We will use the CXMS (chemical cross-linking of proteins coupled with mass spectrometry analysis) analysis to obtain a low-resolution picture. Conjointly, we will use PRE (paramagnetic relaxation enhancement) NMR to further characterize the ensemble structure of LBD dimer, and use SAXS (small-angle x-ray scattering) to assess the relative populations of each conformational state. Based on the structural characterization, we will mutate key interfacial residues that may perturb the ensemble structure of LBD dimer, which will be confirmed by electrophysiological analyses. Together, we will illustrate how the structural change of LBD dimer accompanies the desensitization of GluA2. 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There is no cure and no available treatments to stop this disease progression. Today, mutations in LRRK2 are the most prevalent known genetic causes of Parkinson\u2019s disease, for both familial and sporadic cases. In spite of the intensive efforts over the past decade, the molecular role of LRRK2 in disease pathogenesis, its function, and the effects of disease-causing mutations remain unknown. Understanding the underlying mechanism of LRRK2 normal function and how it is affected by the disease-associated mutations will reveal novel mechanism-based therapeutic strategies. In addition to LRRK2 being associated with PD and being the most promising drug target for the disease, LRRK2 is an immensely intriguing protein, in that it has two enzymatic activities (GTPase activity and Kinase activity) that, together with other non-enzymatic domains, potentially represent a unique example of an intramolecular signaling system. The concept of the Roc GTPase domain functioning as a molecular switch regulating the overall activity of LRRK2 is conceptually interesting from a biochemical perspective, and it is the key to LRRK2\u2019s normal function and disease process. In addition to the relatively wide prevalence of LRRK2 in PD, it is the most attractive target for drug discovery, because over-activation of its kinase activity is linked to disease pathogenesis, and it is an enzyme with active sites well suited for binding potential drugs. Indeed, LRRK2 kinase activity was effectively inhibited by broad kinase inhibitors that compete for ATP in the ATP-binding pocket. However, their translation into the clinic has been difficult due to adverse effects. Various potential alternative strategies are being considered, including targeting the Roc domain. This proposed study seeks to define the structures of ROC domain and its mutants to understand the GTP hydrolysis mechanism and mutations pathogenesis by using X-ray diffraction crystallography, protein biochemistry and biophysics approaches, which could provide insight into locations on LRRK2 structures that are suitable for mechanism-based drug discovery.", "\u8d1f\u8d23\u4eba\u804c\u79f0": "\u526f\u6559\u6388"}, {"h": "", "\u9879\u76ee\u540d\u79f0": "\u7ebf\u6027\u6cdb\u7d20\u94fe\u7ec4\u88c5\u590d\u5408\u7269(LUBAC)\u7684\u8c03\u8282\u673a\u5236\u7814\u7a76", "\u6279\u51c6\u53f7": "31500597", "\u9879\u76ee\u7c7b\u522b": "\u9752\u5e74\u79d1\u5b66\u57fa\u91d1\u9879\u76ee", "\u4f9d\u6258\u5355\u4f4d": "\u4e2d\u56fd\u79d1\u5b66\u9662\u4e0a\u6d77\u6709\u673a\u5316\u5b66\u7814\u7a76\u6240", "\u9879\u76ee\u8d1f\u8d23\u4eba": "\u5218\u5efa\u5e73", "\u8d44\u52a9\u7ecf\u8d39(\u4e07\u5143)": "20", "\u6279\u51c6\u5e74\u5ea6": "2015", "\u5173\u952e\u8bcd": "\u86cb\u767d\u8d28\u590d\u5408\u7269\uff1bX\u5c04\u7ebf\u6676\u4f53\u884d\u5c04\uff1b\u6cdb\u7d20\u5316\uff1b\u80bf\u7624\u574f\u6b7b\u56e0\u5b50TNF\u03b1\uff1b\u7ec6\u80de\u6b7b\u4ea1", "\u662f\u5426\u7ed3\u9898": "\u662f", "\u7814\u7a76\u6210\u679c(\u671f\u520a\u8bba\u6587;\u4f1a\u8bae\u8bba\u6587;\u8457\u4f5c;\u5956\u52b1;\u4e13\u5229)": "4;0;0;0;0", "\u4f9d\u6258\u5355\u4f4dID": "400014", "\u9879\u76ee\u8d1f\u8d23\u4ebaID": "100193226", "\u9879\u76ee\u7c7b\u522b\u4ee3\u7801": "630", "\u7533\u8bf7\u4ee3\u7801": "C050101", "\u8d77\u6b62\u5e74\u6708": "2016-01\u81f32018-12", "\u4e2d\u6587\u6458\u8981": "\u7ebf\u6027\u6cdb\u7d20\u5316\u662f\u4e00\u7c7b\u5e7f\u6cdb\u53c2\u4e0e\u708e\u75c7\u548c\u5148\u5929\u514d\u75ab\u7684\u65b0\u578b\u6cdb\u7d20\u5316\u4fee\u9970\u3002\u8fc4\u4eca\u552f\u4e00\u7684\u7ebf\u6027\u6cdb\u7d20\u94feE3\u8fde\u63a5\u9176LUBAC\u590d\u5408\u7269\u7531\u8c03\u8282\u4e9a\u57faSharpin\u3001HOIL1\u548c\u50ac\u5316\u4e9a\u57faHOIP\u7ec4\u6210\u3002\u5355\u72ec\u7684HOIP\u5904\u4e8e\u81ea\u6291\u5236\u72b6\u6001\uff0c\u4f46\u53ef\u4ee5\u88abSharpin\u6216HOIL1\u6fc0\u6d3b\u3002\u7136\u800c\uff0cHOIP\u7684\u81ea\u6291\u5236\u548c\u6fc0\u6d3b\u3001\u4e0eSharpin\u7684\u76f8\u4e92\u4f5c\u7528\u673a\u5236\u4ecd\u7136\u672a\u77e5\u3002Sharpin\u7f3a\u5931\u5c0f\u9f20\u8868\u73b0\u51fa\u591a\u5668\u5b98\u708e\u75c7\u548cTNF\u03b1\u901a\u8def\u5f02\u5e38\u3002\u4e3a\u4e86\u9610\u660eLUBAC\u590d\u5408\u7269\u7684\u8c03\u63a7\u673a\u5236\uff0c\u672c\u7533\u8bf7\u8ba1\u5212\u89e3\u6790\u81ea\u6291\u5236\u548c\u6fc0\u6d3b\u72b6\u6001\u7684HOIP\u50ac\u5316\u6838\u5fc3\u7247\u6bb5\uff0c\u4ee5\u53caSharpin/HOIP\u590d\u5408\u7269\u7684\u7ed3\u6784\uff0c\u63ed\u793aHOIP\u7684\u81ea\u6291\u5236\u548c\u6fc0\u6d3b\u673a\u5236\uff0c\u5e76\u8bbe\u8ba1\u70b9\u7a81\u53d8\u89e3\u9664\u81ea\u6291\u5236\u6216\u8005\u7834\u574fSharpin\u5bf9HOIP\u7684\u6fc0\u6d3b\uff0c\u7814\u7a76\u76f8\u5e94\u7a81\u53d8\u4f53\u5bf9\u7ec6\u80de\u6b7b\u4ea1\u6216RIP1\u7ebf\u6027\u6cdb\u7d20\u5316\u7684\u5f71\u54cd\uff0c\u4ee5\u68c0\u9a8c\u6211\u4eec\u7684\u5047\u8bf4\uff1aSharpin/HOIP\u590d\u5408\u7269\u5bf9RIP1\u7684\u7ebf\u6027\u6cdb\u7d20\u5316\u51b3\u5b9a\u4e86TNF\u03b1\u901a\u8def\u7684\u6700\u7ec8\u6548\u5e94\u2014\u2014\u708e\u75c7\u6216\u7ec6\u80de\u6b7b\u4ea1\u3002\u73b0\u6709\u5de5\u4f5c\u8fdb\u5c55\u4e3a\u5b9e\u73b0\u4e0a\u8ff0\u76ee\u6807\u5960\u5b9a\u4e86\u575a\u5b9e\u7684\u57fa\u7840\u3002", "\u82f1\u6587\u6458\u8981": "Linear ubiquitination, a recently discovered novel type of ubiquitination, is extensively involved in numerous signaling pathways related to inflammation and innate immune. Linear ubiquitin chain assembly complex (LUBAC) is the sole identified E3 ubiquitin ligase that catalyzes the formation of linear poly-ubiquitin chain. It consists of two regulatory subunits Sharpin and HOIL1 as well as one catalytic subunit HOIP. The isolated HOIP is in an auto-inhibited state, but it can be activated by Sharpin or HOIL1 to sufficiently promote the linear ubiquitination of target substrates. However, the molecular mechanisms underlying the the auto-inhibition of HOIP, its activation by Sharpin or HOIL1, and the interaction between HOIP and Sharpin are largely unknown. Previous studies indicated that loss of Sharpin in the mouse caused immunodeficiency and multi-organ inflammation, and severely inhibited the linear ubiquitination of TNF\u03b1 receptor signaling complex. Based on these findings, we propose a hypothesis: the linear ubiquitination level of RIP1 catalyzed by Sharpin/HOIP complex determines the outcome of TNF\u03b1 signaling\u2014inflammation or cell death. To further understand the regulatory mechanism of LUBAC complex, we aimed to solve the structures of the catalytic fragment of HOIP either in auto-inhibited or in activated states as well as the Sharpin/HOIP complex, thereby to uncover the auto-inhibition and activation mechanism of HOIP. Based on the solved structures, we will design point mutations to specifically disrupt the auto-inhibition or the trans-activation of HOIP mediated by Sharpin; we will further test our hypothesis by assessing the impact of these mutations on the linear ubiquitination level of RIP1 and the TNF\u03b1 induced cell death. Our current research progress has laid the foundation for us to pursue the scientific goals in this proposal.", "\u8d1f\u8d23\u4eba\u804c\u79f0": "\u526f\u7814\u7a76\u5458"}, {"h": "", "\u9879\u76ee\u540d\u79f0": "\u8f6c\u5f55\u56e0\u5b50CcmR\u8c03\u63a7\u84dd\u7ec6\u83cc\u78b3\u6d53\u7f29\u673a\u5236\u7684\u7ed3\u6784\u751f\u7269\u5b66\u57fa\u7840", "\u6279\u51c6\u53f7": "31500598", "\u9879\u76ee\u7c7b\u522b": "\u9752\u5e74\u79d1\u5b66\u57fa\u91d1\u9879\u76ee", "\u4f9d\u6258\u5355\u4f4d": "\u4e2d\u56fd\u79d1\u5b66\u6280\u672f\u5927\u5b66", "\u9879\u76ee\u8d1f\u8d23\u4eba": "\u6210\u671b", "\u8d44\u52a9\u7ecf\u8d39(\u4e07\u5143)": "20", "\u6279\u51c6\u5e74\u5ea6": "2015", "\u5173\u952e\u8bcd": "\u84dd\u85fb\uff1b\u78b3\u6d53\u7f29\u673a\u5236\uff1b\u8f6c\u5f55\u8c03\u63a7\uff1b\u6676\u4f53\u7ed3\u6784\uff1b\u5f02\u6784\u6548\u5e94", "\u662f\u5426\u7ed3\u9898": "\u662f", "\u7814\u7a76\u6210\u679c(\u671f\u520a\u8bba\u6587;\u4f1a\u8bae\u8bba\u6587;\u8457\u4f5c;\u5956\u52b1;\u4e13\u5229)": "1;0;0;0;0", "\u4f9d\u6258\u5355\u4f4dID": "200654", "\u9879\u76ee\u8d1f\u8d23\u4ebaID": "100047316", "\u9879\u76ee\u7c7b\u522b\u4ee3\u7801": "630", "\u7533\u8bf7\u4ee3\u7801": "C050101", "\u8d77\u6b62\u5e74\u6708": "2016-01\u81f32018-12", "\u4e2d\u6587\u6458\u8981": "\u84dd\u7ec6\u83cc\u662f\u88ab\u5e7f\u6cdb\u7528\u4e8e\u5149\u5408\u4f5c\u7528\u548c\u78b3\u6d53\u7f29\u673a\u5236(CO2-concentrating mechanism, CCM)\u7814\u7a76\u7684\u91cd\u8981\u6a21\u5f0f\u751f\u7269\u3002CcmR\u662f\u96c6\u80de\u85fbPCC6803\u4e2d\u7684\u4e00\u4e2a\u8c03\u63a7\u78b3\u6d53\u7f29\u673a\u5236\u7684\u5168\u5c40\u6027\u8f6c\u5f55\u56e0\u5b50\uff0c\u5728\u4f4e\u78b3\u4fe1\u53f7\u4e0b\u89e3\u9664\u5bf9CCM\u76f8\u5173\u57fa\u56e0\u7684\u6291\u5236\uff0c\u5f15\u8d77\u8868\u8fbe\u4e0a\u8c03\uff0c\u4fc3\u8fdbCO2\u7684\u5438\u6536\uff0c\u4fdd\u8bc1\u5149\u5408\u4f5c\u7528\u7684\u987a\u5229\u8fdb\u884c\u3002\u6211\u4eec\u5c06\u4ee5CcmR apo-form\u56db\u805a\u4f53\u6676\u4f53\u7ed3\u6784\u4e3a\u57fa\u7840\uff0c\u7efc\u5408\u5229\u7528\u751f\u7269\u4fe1\u606f\u5b66\u3001\u751f\u7269\u5316\u5b66\u3001\u5206\u5b50\u751f\u7269\u5b66\u4ee5\u53ca\u7ed3\u6784\u751f\u7269\u5b66\u624b\u6bb5\uff0c\u5bf9CcmR\u4e0eDNA\u548c/\u6216\u4fe1\u53f7\u5206\u5b50\u7684\u76f8\u4e92\u4f5c\u7528\u53ca\u5176\u4e8c\u5143\u548c\u4e09\u5143\u6676\u4f53\u7ed3\u6784\u8fdb\u884c\u7cfb\u7edf\u7814\u7a76\uff0c\u4ee5\u671f\u63ed\u793aCcmR\u7684\u522b\u6784\u673a\u7406\uff0c\u5e76\u57fa\u4e8eCcmR\u7279\u5f02\u6027\u8bc6\u522b\u7684DNA\u5e8f\u5217\u9274\u5b9a\u5176\u8c03\u63a7\u7684\u4e0b\u6e38\u57fa\u56e0\u7f51\u7edc\u3002\u8be5\u9879\u76ee\u5c06\u9610\u660eCcmR\u7684\u8c03\u63a7\u78b3\u6d53\u7f29\u673a\u5236\u7684\u7ed3\u6784\u57fa\u7840\uff0c\u6709\u671b\u4e3a\u751f\u6001\u5e73\u8861\u548c\u519c\u4e1a\u751f\u4ea7\u63d0\u4f9b\u7406\u8bba\u6307\u5bfc\u3002", "\u82f1\u6587\u6458\u8981": "Cyanobacterium is an ideal model for studying the photosynthesis and CO2-concentration mechanism (CCM). The transcriptional factor CcmR was first identified in the cyanobacterium Synechocystis sp. PCC6803. It serves as a global controller to increase the expression of CCM related genes, which are suppressed at a high Ci concentration, thus augmenting the uptake of CO2 for the efficacy photosynthesis. Based on our previously determined crystal structure of the apo-form CcmR tetramer, we will systematically investigate the interactions of CcmR with the putative allosteric molecule and its binding DNA, by combining the methodologies of bioinformatics, biochemistry, molecular biology and structural biology. The findings will enable us to elucidate the CcmR allosteric mechanism, and to identify the gene network under the control of CcmR. This project will provide insights into the CCM regulated by CcmR, and might be helpful for guiding the ecological balance control and agricultural production in the future.", "\u8d1f\u8d23\u4eba\u804c\u79f0": "\u535a\u58eb\u540e"}, {"h": "", "\u9879\u76ee\u540d\u79f0": "\u4e09\u7ef4\u8d85\u5206\u8fa8\u6280\u672f\u7814\u7a76\u7ec6\u80de\u6838\u5b54\u590d\u5408\u7269\u7684\u9009\u62e9\u6027\u5c4f\u969c\u5206\u5e03", "\u6279\u51c6\u53f7": "31500599", "\u9879\u76ee\u7c7b\u522b": "\u9752\u5e74\u79d1\u5b66\u57fa\u91d1\u9879\u76ee", "\u4f9d\u6258\u5355\u4f4d": "\u590d\u65e6\u5927\u5b66", "\u9879\u76ee\u8d1f\u8d23\u4eba": "\u9a6c\u70af", "\u8d44\u52a9\u7ecf\u8d39(\u4e07\u5143)": "21", "\u6279\u51c6\u5e74\u5ea6": "2015", "\u5173\u952e\u8bcd": "\u7ec6\u80de\u6838\u5b54\u590d\u5408\u7269\uff1bFG\u5c4f\u969c\uff1b\u5355\u5206\u5b50\uff1b\u8d85\u5206\u8fa8\u663e\u5fae\u955c\uff1b\u6838\u5b54\u4f20\u8f93", "\u662f\u5426\u7ed3\u9898": "\u662f", "\u7814\u7a76\u6210\u679c(\u671f\u520a\u8bba\u6587;\u4f1a\u8bae\u8bba\u6587;\u8457\u4f5c;\u5956\u52b1;\u4e13\u5229)": "9;0;0;0;0", "\u4f9d\u6258\u5355\u4f4dID": "201361", "\u9879\u76ee\u8d1f\u8d23\u4ebaID": "100162892", "\u9879\u76ee\u7c7b\u522b\u4ee3\u7801": "630", "\u7533\u8bf7\u4ee3\u7801": "C050101", "\u8d77\u6b62\u5e74\u6708": "2016-01\u81f32018-12", "\u4e2d\u6587\u6458\u8981": "\u7ec6\u80de\u6838\u5b54\u590d\u5408\u7269\uff08NPC\uff09\u662f\u771f\u6838\u7ec6\u80de\u4e2d\u8fde\u63a5\u7ec6\u80de\u8d28\u548c\u7ec6\u80de\u6838\u4e4b\u95f4\u7684\u9009\u62e9\u6027\u53cc\u5411\u901a\u9053\u3002\u7531\u5bcc\u542b\u82ef\u4e19\u6c28\u9178-\u7518\u6c28\u9178\uff08FG\uff09\u6c28\u57fa\u9178\u7247\u6bb5\u7684\u81ea\u7136\u975e\u6298\u53e0\u86cb\u767d\u6784\u6210\u7684FG-\u5c4f\u969c,\u9009\u62e9\u6027\u5730\u8c03\u63a7\u57fa\u56e0\u76f8\u5173\u7269\u8d28,\u6309\u7167\u88ab\u52a8\u8fd0\u8f93\u6216\u8005\u4e3b\u52a8\u4ecb\u5165\u8fd0\u8f93\u7684\u65b9\u5f0f\u8fdb\u51fa\u7ec6\u80de\u6838\u3002\u7136\u800c\uff0c\u6838\u5b54\u5185FG\u5c4f\u969c\u95f4\u7684\u76f8\u4e92\u4f5c\u7528\u4ee5\u53ca\u5206\u5e03\u72b6\u51b5\u4ecd\u7136\u662f\u6781\u5177\u4e89\u8bae\u7684\u91cd\u8981\u79d1\u5b66\u95ee\u9898\u3002\u672c\u9879\u76ee\u5c06\u57fa\u4e8e\u7533\u8bf7\u4eba\u53d1\u660e\u7684\u5355\u70b9\u659c\u5165\u5c04\u6fc0\u53d1\u5feb\u901f\u8d85\u5206\u8fa8\u663e\u5fae\u955c\u6280\u672f\uff0c\u7814\u7a76\u6838\u5b54\u4f20\u8f93\u86cb\u767d\u6216FG-\u86cb\u767d\u7247\u6bb5\u4e0eFG\u5c4f\u969c\u53cd\u5e94\u7684\u4e09\u7ef4\u5206\u5e03\u56fe\u50cf\uff0c\u4ece\u800c\u83b7\u5f97FG-\u5c4f\u969c\u5728\u7ec6\u80de\u6838\u5b54\u5185\u5b8c\u6574\u7684\u5206\u5e03\u60c5\u51b5\u3002\u53e6\u5916,\u8fdb\u4e00\u6b65\u68c0\u6d4b\u6838\u5b54\u4f20\u8f93\u86cb\u767d\u5bf9FG\u5c4f\u969c\u7684\u5206\u5e03\u5f71\u54cd\uff0c\u8ba8\u8bba\u6838\u5b54\u4f20\u8f93\u7684\u81ea\u8c03\u63a7\u673a\u5236\u3002\u8fd8\u5c06\u4ece\u4e0d\u540c\u4f20\u8f93\u86cb\u767d\u6216FG-\u7247\u6bb5\u5728\u4f20\u8f93\u8fc7\u7a0b\u4e2d\u7684\u7ade\u4e89\u6548\u679c\uff0c\u8ba8\u8bbaFG\u5c4f\u969c\u5bf9\u5404\u7c7b\u57fa\u56e0\u76f8\u5173\u7269\u8d28\u4f20\u8f93\u7684\u4f18\u5148\u987a\u5e8f\u3002\u6700\u7ec8\uff0c\u5b8c\u6574\u7684\u4e09\u7ef4FG\u5c4f\u969c\u5c06\u5bf9\u6838\u5b54\u86cb\u767d\u7f3a\u5931\u76f8\u5173\u7684\u767d\u8840\u75c5\u3001\u963f\u5c14\u5179\u6d77\u9ed8\u75c7\u7684\u81f4\u75c5\u673a\u5236\uff0c\u4ee5\u53ca\u5404\u79cd\u7c7b\u75c5\u6bd2\u7684\u4fb5\u5165\u673a\u5236\u7b49\u6838\u5b54\u76f8\u5173\u75c5\u7406\u673a\u5236\u6216\u57fa\u56e0\u6cbb\u7597\u63d0\u4f9b\u4fe1\u606f\u3002", "\u82f1\u6587\u6458\u8981": "The nuclear pore complexes (NPCs) selectively mediate the bidirectional trafficking of macromolecules between the cytoplasm and the nucleus in eukaryotic cells. The selective barrier formed by natively unfolded phenylalanine-glycine (FG) nucleoporins (Nups) inside the NPC allows for passive and facilitated transport through the NPC. However, the interactions that form the FG-barrier and their spatial distribution in the NPC remain unresolved. Based on the single-point edge-excitation sub-diffusion (SPEED) microscopy techniques, the applicant's invention, three-dimensionally map the interaction distributions between the fluorescent transport receptors (TRs) or FG-fragment and FG barrier. Then, we obtain fully information of the FG-barrier distribution in the NPC. The conformation change of the FG-barrier by TRs would be discussed as self-regulating mechanism of nucleocytoplasmic transport. Also from the competitive effects during different FG-fragments and transport proteins during the transport discuss priorities for the various gene related transport. Finally\uff0cthe complete three-dimensional FG-barrier distribution will provide information with leukemia, Alzheimer's disease pathogenesis, as well as various types of viruses invade mechanisms for NPC related pathological mechanism or gene therapy.", "\u8d1f\u8d23\u4eba\u804c\u79f0": "\u7814\u7a76\u5458"}, {"h": "", "\u9879\u76ee\u540d\u79f0": "\u6210\u808c\u7ec6\u80de\u878d\u5408\u86cb\u767dmyomaker\u7684\u7ed3\u6784\u57fa\u7840\u4e0e\u4f5c\u7528\u673a\u7406", "\u6279\u51c6\u53f7": "31500600", "\u9879\u76ee\u7c7b\u522b": "\u9752\u5e74\u79d1\u5b66\u57fa\u91d1\u9879\u76ee", "\u4f9d\u6258\u5355\u4f4d": "\u6e05\u534e\u5927\u5b66", "\u9879\u76ee\u8d1f\u8d23\u4eba": "\u9f9a\u5fb7\u987a", "\u8d44\u52a9\u7ecf\u8d39(\u4e07\u5143)": "9", "\u6279\u51c6\u5e74\u5ea6": "2015", "\u5173\u952e\u8bcd": "\u819c\u86cb\u767d\uff1b\u5747\u4e00\u6027\uff1b\u6676\u4f53\u7b5b\u9009\uff1b\u7ed3\u6784\u89e3\u6790\uff1b\u6676\u4f53\u7ed3\u6784", "\u662f\u5426\u7ed3\u9898": "\u662f", "\u7814\u7a76\u6210\u679c(\u671f\u520a\u8bba\u6587;\u4f1a\u8bae\u8bba\u6587;\u8457\u4f5c;\u5956\u52b1;\u4e13\u5229)": "0;0;0;0;0", "\u4f9d\u6258\u5355\u4f4dID": "201260", "\u9879\u76ee\u8d1f\u8d23\u4ebaID": "100177698", "\u9879\u76ee\u7c7b\u522b\u4ee3\u7801": "630", "\u7533\u8bf7\u4ee3\u7801": "C050101", "\u8d77\u6b62\u5e74\u6708": "2016-01\u81f32016-12", "\u4e2d\u6587\u6458\u8981": "Myomaker\u662f\u65b0\u53d1\u73b0\u7684\u4e00\u79cd\u53ef\u4ee5\u76f4\u63a5\u8c03\u63a7\u6210\u808c\u7ec6\u80de\u878d\u5408\u548c\u808c\u8089\u518d\u751f\u7684\u86cb\u767d\uff0c\u8fd9\u662f\u54fa\u4e73\u52a8\u7269\u7ec6\u80de\u4e2d\u552f\u4e00\u4e00\u4e2a\u88ab\u9274\u5b9a\u7684\u808c\u8089\u7279\u5f02\u6027\u7684\u8c03\u8282\u86cb\u767d\u3002\u5b83\u4fc3\u8fdb\u6210\u808c\u7ec6\u80de\u878d\u5408\u4ee5\u53ca\u808c\u8089\u518d\u751f\u7684\u6d3b\u6027\u4e3a\u53d7\u4f24\u540e\u7684\u808c\u8089\u518d\u751f\u63d0\u4f9b\u4e86\u65b0\u7684\u673a\u4f1a\uff0c\u4e3a\u808c\u8089\u6027\u75be\u75c5\u7684\u6cbb\u7597\u63d0\u4f9b\u4e86\u65b0\u7684\u601d\u8def\u3002\u7136\u800c\uff0c\u76ee\u524d\u5bf9\u5176\u53d1\u6325\u529f\u80fd\u7684\u5206\u5b50\u673a\u7406\u4ecd\u7136\u4e00\u65e0\u6240\u77e5\u3002\u672c\u9879\u76ee\u62df\u4ece\u7ed3\u6784\u751f\u7269\u5b66\u7684\u89d2\u5ea6\u51fa\u53d1\uff0c\u89e3\u6790\u5176\u6676\u4f53\u7ed3\u6784\uff0c\u63ed\u793a\u5176\u5206\u5b50\u4f5c\u7528\u673a\u7406\u3002", "\u82f1\u6587\u6458\u8981": "Myomaker, a new discovered myoblast fusion activator, which is the only identified muscle-specific protein that directly regulates myoblast fusion and muscle regeneration in mammals. These activities of myomaker provide new opportunities for muscle regeneration and new strategies for therapy of muscle diseases. However, the molecular mechanism of myomaker is still in the dark. The aim of this project is to determinate the crystal structure of myomaker and provide new insights into the functional mechanism of myomaker.", "\u8d1f\u8d23\u4eba\u804c\u79f0": "\u535a\u58eb\u540e"}, {"h": "", "\u9879\u76ee\u540d\u79f0": "\u5e03\u6c0f\u9525\u866b\u4e2d\u53c2\u4e0e\u57fa\u56e0\u8f6c\u5f55\u8c03\u63a7\u7684PAF1\u590d\u5408\u7269\u7684\u7ed3\u6784\u548c\u529f\u80fd\u7814\u7a76", "\u6279\u51c6\u53f7": "31500601", "\u9879\u76ee\u7c7b\u522b": "\u9752\u5e74\u79d1\u5b66\u57fa\u91d1\u9879\u76ee", "\u4f9d\u6258\u5355\u4f4d": "\u4e2d\u56fd\u79d1\u5b66\u6280\u672f\u5927\u5b66", "\u9879\u76ee\u8d1f\u8d23\u4eba": "\u5ed6\u5584\u6656", "\u8d44\u52a9\u7ecf\u8d39(\u4e07\u5143)": "20", "\u6279\u51c6\u5e74\u5ea6": "2015", "\u5173\u952e\u8bcd": "PAF1\u590d\u5408\u7269\uff1b\u8f6c\u5f55\u8c03\u63a7\uff1b\u5e03\u6c0f\u9525\u866b\uff1b\u86cb\u767d\u8d28\u7ed3\u6784\uff1b\u86cb\u767d\u8d28\u76f8\u4e92\u4f5c\u7528", "\u662f\u5426\u7ed3\u9898": "\u662f", "\u7814\u7a76\u6210\u679c(\u671f\u520a\u8bba\u6587;\u4f1a\u8bae\u8bba\u6587;\u8457\u4f5c;\u5956\u52b1;\u4e13\u5229)": "11;0;0;0;1", "\u4f9d\u6258\u5355\u4f4dID": "200654", "\u9879\u76ee\u8d1f\u8d23\u4ebaID": "100186764", "\u9879\u76ee\u7c7b\u522b\u4ee3\u7801": "630", "\u7533\u8bf7\u4ee3\u7801": "C050101", "\u8d77\u6b62\u5e74\u6708": "2016-01\u81f32018-12", "\u4e2d\u6587\u6458\u8981": "\u771f\u6838\u751f\u7269\u57fa\u56e0\u8f6c\u5f55\u7684\u8c03\u63a7\u5728\u65f6\u95f4\u548c\u7a7a\u95f4\u4e0a\u90fd\u5177\u6709\u5f88\u9ad8\u7684\u590d\u6742\u5ea6\uff0c\u7ec6\u80de\u5185\u57fa\u56e0\u8f6c\u5f55\u8c03\u8282\u7684\u5f02\u5e38\u4e0e\u5404\u7c7b\u75be\u75c5\u5bc6\u5207\u76f8\u5173\u3002\u5728\u7814\u7a76\u8f6c\u5f55\u8c03\u8282\u7684\u8fc7\u7a0b\u4e2d\uff0c\u5927\u91cfRNA\u805a\u5408\u9176\u76f8\u5173\u86cb\u767d\u590d\u5408\u4f53\u88ab\u62a5\u9053\uff0c\u5176\u4e2dPAF1\u590d\u5408\u7269\uff08RNA polymerase II associated factor complex, PAF1C\uff09\u5c31\u662f\u6700\u8fd1\u53d1\u73b0\u7684\u4e00\u79cd\u3002PAF1\u590d\u5408\u7269\u542b\u6709\u81f3\u5c11 5\u4e2a\u4e0d\u540c\u7684\u86cb\u767d\u4e9a\u57fa\uff0c\u80fd\u591f\u534f\u540c\u5176\u4ed6\u7684\u8f6c\u5f55\u56e0\u5b50\u53ca\u7ec4\u86cb\u767d\u4fee\u9970\u9176\u6765\u8c03\u63a7\u8f6c\u5f55\u8fc7\u7a0b\u3002\u9525\u866b\u662f\u4e00\u7c7b\u5355\u7ec6\u80de\u771f\u6838\u539f\u751f\u751f\u7269\uff0c\u80fd\u591f\u5f15\u8d77\u591a\u79cd\u9525\u866b\u75c5\u3002\u76ee\u524d\u5728\u5e03\u6c0f\u9525\u866b\u5c5e\u4e2d\u53d1\u73b0\u7684PAF1\u590d\u5408\u4f53\u7ec4\u6210\u4e0e\u9ad8\u7b49\u771f\u6838\u751f\u7269\u4e0d\u5b8c\u5168\u4fdd\u5b88\uff0c\u53ef\u80fd\u6697\u793a\u4e86\u5e03\u6c0f\u9525\u866b\u7279\u6709\u7684\u57fa\u56e0\u8f6c\u5f55\u8c03\u8282\u65b9\u5f0f\u3002\u672c\u9879\u7814\u7a76\u5c06\u7ed3\u5408\u7ed3\u6784\u751f\u7269\u5b66\u548c\u7ec6\u80de\u751f\u7269\u5b66\u65b9\u6cd5\uff0c\u7814\u7a76\u5e03\u6c0f\u9525\u866b\u4e2dPAF1\u590d\u5408\u7269\u7684\u7ed3\u6784\u53ca\u5176\u5728\u57fa\u56e0\u8f6c\u5f55\u8c03\u63a7\u4e2d\u7684\u4f5c\u7528\u3002\u672c\u7814\u7a76\u4e0d\u4ec5\u5c06\u4e30\u5bcc\u6211\u4eec\u5bf9\u5e03\u6c0f\u9525\u866bPAF1\u590d\u5408\u7269\u548c\u57fa\u56e0\u8f6c\u5f55\u8c03\u63a7\u7684\u8ba4\u8bc6\uff0c\u5bf9\u4e8e\u6211\u4eec\u4e86\u89e3\u771f\u6838\u751f\u7269PAF1\u590d\u5408\u7269\u548c\u57fa\u56e0\u8f6c\u5f55\u8c03\u63a7\u7684\u8fdb\u5316\u4e5f\u5177\u6709\u91cd\u8981\u610f\u4e49\u3002", "\u82f1\u6587\u6458\u8981": "Eukaryotic gene transcription regulation is extremely complex in space and time. Any defect of transcription process is closely related to a variety of diseases. Many protein complexes have been reported during the study of transcription regulation, PAF1C (RNA polymerase II associated factor 1 complex) is such a complex discovered recently. PAF1C, contains at least 5 subunits. It participates in gene transcription regulation cooperatively with other transcription factors and histone modification enzymes. Trypanosomatids, the causative pathogens of trypanosomiasis, are a group of unicellular protozoa. The compositions of PAF1C of Trypanosoma brucei (T. brucei) is not fully conserved with that from higher eukaryotes, which may imply species-specific regulation pathway of gene transcription. Here, we are trying to explore the structure of PAF1C and its role in gene transcription regulation in T. brucei, by combining the techniques of structural biology and cell biology. This study will not only enrich our knowledge of PAF1C\u2019s role in transcription regulation in T. brucei, but also has important implications for our understanding of the evolution of eukaryotic PAF1 complex and gene transcription regulation.", "\u8d1f\u8d23\u4eba\u804c\u79f0": "\u526f\u7814\u7a76\u5458"}, {"h": "", "\u9879\u76ee\u540d\u79f0": "\u94dc\u7eff\u5fae\u56ca\u85fb\u6c14\u56ca\u86cb\u767d\u7684\u7ed3\u6784\u548c\u529f\u80fd\u7814\u7a76", "\u6279\u51c6\u53f7": "31500602", "\u9879\u76ee\u7c7b\u522b": "\u9752\u5e74\u79d1\u5b66\u57fa\u91d1\u9879\u76ee", "\u4f9d\u6258\u5355\u4f4d": "\u4e2d\u56fd\u79d1\u5b66\u6280\u672f\u5927\u5b66", "\u9879\u76ee\u8d1f\u8d23\u4eba": "\u4ee3\u4e9a\u7537", "\u8d44\u52a9\u7ecf\u8d39(\u4e07\u5143)": "20", "\u6279\u51c6\u5e74\u5ea6": "2015", "\u5173\u952e\u8bcd": "\u94dc\u7eff\u5fae\u56ca\u85fb\uff1b\u6c14\u56ca\uff1b\u6c14\u56ca\u86cb\u767d\uff1b\u6676\u4f53\u7ed3\u6784\uff1b\u7ed3\u6784\u86cb\u767d", "\u662f\u5426\u7ed3\u9898": "\u662f", "\u7814\u7a76\u6210\u679c(\u671f\u520a\u8bba\u6587;\u4f1a\u8bae\u8bba\u6587;\u8457\u4f5c;\u5956\u52b1;\u4e13\u5229)": "0;0;0;0;0", "\u4f9d\u6258\u5355\u4f4dID": "200654", "\u9879\u76ee\u8d1f\u8d23\u4ebaID": "100047317", "\u9879\u76ee\u7c7b\u522b\u4ee3\u7801": "630", "\u7533\u8bf7\u4ee3\u7801": "C050101", "\u8d77\u6b62\u5e74\u6708": "2016-01\u81f32018-12", "\u4e2d\u6587\u6458\u8981": "\u94dc\u7eff\u5fae\u56ca\u85fb\u662f\u4e00\u79cd\u5355\u7ec6\u80de\u6d6e\u6e38\u84dd\u85fb\uff0c\u80fd\u5927\u91cf\u4ea7\u751f\u6c14\u56ca\uff0c\u8425\u517b\u4e30\u5bcc\u65f6\u5728\u6de1\u6c34\u6c34\u4f53\u8868\u9762\u805a\u96c6\u66b4\u53d1\u6c34\u534e\u3002\u6c14\u56ca\u662f\u4e00\u79cd\u5b8c\u5168\u7531\u86cb\u767d\u8d28\u7ec4\u6210\u7684\u4e2d\u7a7a\u3001\u5145\u6ee1\u6c14\u4f53\u7684\u60f0\u6027\u7ed3\u6784\u3002\u6c14\u56ca\u4e3a\u85fb\u7ec6\u80de\u63d0\u4f9b\u6d6e\u529b\uff0c\u4f7f\u5176\u81ea\u884c\u8c03\u8282\u5728\u81ea\u7136\u6c34\u4f53\u4e2d\u7684\u5782\u76f4\u4f4d\u7f6e\uff0c\u6f02\u6d6e\u5230\u6c27\u6c14\u548c\u5149\u7167\u90fd\u9002\u5b9c\u7684\u4f4d\u7f6e\u4ee5\u5229\u4e8e\u81ea\u8eab\u751f\u957f\u548c\u751f\u5883\u6b96\u6c11\u5316\u3002\u6c14\u56ca\u4e0d\u4ec5\u662f\u94dc\u7eff\u5fae\u56ca\u85fb\u80fd\u6210\u4e3a\u4f18\u52bf\u85fb\u79cd\u7684\u91cd\u8981\u539f\u56e0\u4e4b\u4e00\uff0c\u4e5f\u5728\u6c34\u534e\u7684\u66b4\u53d1\u8fc7\u7a0b\u4e2d\u8d77\u5230\u4e86\u8c03\u8282\u4f5c\u7528\u3002\u7136\u800c\uff0c\u4eba\u4eec\u81f3\u4eca\u5c1a\u672a\u5f04\u6e05\u6c14\u56ca\u7684\u7ed3\u6784\u53ca\u5176\u5408\u6210\u964d\u89e3\u673a\u5236\u3002\u4e3a\u4e86\u63a2\u7a76\u6c14\u56ca\u5408\u6210\u76f8\u5173\u86cb\u767d\u7684\u4e09\u7ef4\u7ed3\u6784\uff0c\u8fdb\u4e00\u6b65\u91cd\u6784\u6c14\u56ca\u8fd9\u4e00\u4e2d\u7a7a\u7ed3\u6784\u7684\u4e09\u7ef4\u9762\u8c8c\uff0c\u6211\u4eec\u4ee5\u94dc\u7eff\u5fae\u56ca\u85fbMicrocystis aeruginosa PCC 7806\u4e2d\u7684\u6c14\u56ca\u5408\u6210\u76f8\u5173\u7684\u4e00\u7ec4Gvp\u86cb\u767d\u4e3a\u7814\u7a76\u5bf9\u8c61\uff0c\u5229\u7528X\u5c04\u7ebf\u6676\u4f53\u5b66\u624b\u6bb5\u89e3\u6790\u5404\u4e2a\u6c14\u56ca\u86cb\u767d\u7684\u7ed3\u6784\uff0c\u5e76\u8054\u5408\u8fd0\u7528\u9ad8\u5206\u8fa8\u7387\u51b7\u51bb\u7535\u955c\uff0c\u86cb\u767d\u8d28\u514d\u75ab\u5370\u8ff9\u6cd5\u548c\u80f6\u4f53\u91d1\u6807\u8bb0\u7b49\u65b9\u6cd5\u6765\u5206\u6790\u5404\u7ed3\u6784\u86cb\u767d\u7684\u5177\u4f53\u5b9a\u4f4d\u3002\u8be5\u9879\u76ee\u5c06\u89e3\u6790\u6c14\u56ca\u539f\u5b50\u5206\u8fa8\u7387\u6c34\u5e73\u4e0a\u7684\u4e09\u7ef4\u7ed3\u6784\uff0c\u5bf9\u6cbb\u7406\u6c34\u534e\u66b4\u53d1\u6709\u4e00\u5b9a\u7406\u8bba\u6307\u5bfc\u610f\u4e49\u3002", "\u82f1\u6587\u6458\u8981": "Microcystis aeruginosa was investigated and identified as a planktonic unicellular cyanobacterium which is responsible for algal bloom in the freshwater environments. In Microcystis cells, an abundant production of intracellular structures, the gas vesicle, an inert, hollow and gas-filled structure, formed solely from proteins, provides cells with buoyancy and regulates their vertical distribution in natural waters. Cyanobacteria could float taxis toward air-liquid interfaces of water environments, positioning themselves at a depth with optimal light and oxygen supply for better growth, subsequent niche colonization and water-bloom formation. However, the fine structure of gas vesicle and its  biosynthesis/degradation mechanisms are still unclear. To determine three dimensional structures of gas vesicle proteins and remodeling the integral hollow structure, we are committed to solve structures of Gvp proteins from Microcystis aeruginosa PCC 7806 using X-ray crystallography. Moreover, in combination with high-resolution cryo-electron microscopy, we will investigate the localization of individual Gvp proteins by immunoblotting and immunogold labeling-based tomography. These findings will provide insights into structural characteristics of gas vesicle and the rational control of algal bloom.", "\u8d1f\u8d23\u4eba\u804c\u79f0": "\u535a\u58eb\u540e"}, {"h": "", "\u9879\u76ee\u540d\u79f0": "\u819c\u73af\u5883\u5bf9\u819c\u86cb\u767dDAGK\u7ed3\u6784\u4e0e\u529f\u80fd\u7684\u5f71\u54cd", "\u6279\u51c6\u53f7": "31500603", "\u9879\u76ee\u7c7b\u522b": "\u9752\u5e74\u79d1\u5b66\u57fa\u91d1\u9879\u76ee", "\u4f9d\u6258\u5355\u4f4d": "\u4e2d\u56fd\u79d1\u5b66\u9662\u6b66\u6c49\u7269\u7406\u4e0e\u6570\u5b66\u7814\u7a76\u6240", "\u9879\u76ee\u8d1f\u8d23\u4eba": "\u9648\u8273\u53ef", "\u8d44\u52a9\u7ecf\u8d39(\u4e07\u5143)": "20", "\u6279\u51c6\u5e74\u5ea6": "2015", "\u5173\u952e\u8bcd": "\u819c\u86cb\u767d\u7ed3\u6784\uff1b\u56fa\u4f53\u6838\u78c1\u5171\u632f\uff1b\u5929\u7136\u819c\uff1b\u53bb\u57a2\u5242\uff1b\u7518\u6cb9\u4e8c\u8102\u6fc0\u9176", "\u662f\u5426\u7ed3\u9898": "\u662f", "\u7814\u7a76\u6210\u679c(\u671f\u520a\u8bba\u6587;\u4f1a\u8bae\u8bba\u6587;\u8457\u4f5c;\u5956\u52b1;\u4e13\u5229)": "3;0;0;0;0", "\u4f9d\u6258\u5355\u4f4dID": "201322", "\u9879\u76ee\u8d1f\u8d23\u4ebaID": "100150871", "\u9879\u76ee\u7c7b\u522b\u4ee3\u7801": "630", "\u7533\u8bf7\u4ee3\u7801": "C050101", "\u8d77\u6b62\u5e74\u6708": "2016-01\u81f32018-12", "\u4e2d\u6587\u6458\u8981": "\u819c\u86cb\u767d\u7684\u7ed3\u6784\u4e0e\u529f\u80fd\u6df1\u53d7\u6240\u5904\u73af\u5883\u7684\u5f71\u54cd\u3002\u76ee\u524d\uff0c\u5728PDB\u6570\u636e\u5e93\u4e2d\u6536\u5f55\u7684\u819c\u86cb\u767d\u7ed3\u678490%\u4ee5\u4e0a\u662f\u5728\u819c\u6a21\u62df\u73af\u5883\u2014\u53bb\u57a2\u5242\u80f6\u675f\u4e2d\u89e3\u6790\u7684\u3002\u7136\u800c\uff0c\u5728\u53bb\u57a2\u5242\u7684\u73af\u5883\u4e2d\uff0c\u819c\u86cb\u767d\u7684\u771f\u5b9e\u7ed3\u6784\u80fd\u5426\u88ab\u7ef4\u6301\u662f\u5907\u53d7\u7ed3\u6784\u751f\u7269\u5b66\u5bb6\u5173\u6ce8\u7684\u95ee\u9898\u3002\u5927\u80a0\u6746\u83cc\u7518\u6cb9\u4e8c\u8102\u6fc0\u9176(DAGK)\u662f\u4e00\u4e2a\u5f88\u91cd\u8981\u7684\u4e09\u8de8\u819c\u86cb\u767d\uff0c\u5176\u4e09\u7ef4\u7ed3\u6784\u5df2\u7ecf\u88ab\u6db2\u4f53\u6838\u78c1\u5171\u632f\u548cX-Ray\u6676\u4f53\u884d\u5c04\u7684\u65b9\u6cd5\u5728\u53bb\u57a2\u5242\u80f6\u675f\u6216\u8102\u8d28\u7acb\u65b9\u76f8\u4e2d\u6240\u89e3\u6790\uff0c\u7136\u800c\u7531\u4e8e\u73af\u5883\u7684\u4e0d\u540c\uff0c\u5f97\u5230\u7684\u7ed3\u6784\u5dee\u522b\u5f88\u5927\uff0c\u5e76\u4e14\u8fd9\u4e24\u79cd\u7ed3\u6784\u90fd\u4e0d\u662f\u5728DAGK\u7684\u5929\u7136\u819c\u73af\u5883\u4e2d\u8fdb\u884c\u89e3\u6790\u7684\u3002\u56fa\u4f53\u6838\u78c1\u5171\u632f\u6280\u672f\u53ef\u4ee5\u5728\u63a5\u8fd1\u819c\u86cb\u767d\u5929\u7136\u73af\u5883\u7684\u78f7\u8102\u53cc\u5c42\u819c\u4e2d\u89e3\u6790\u5176\u4e09\u7ef4\u7ed3\u6784\uff0c\u662f\u6d4b\u5b9a\u4e0e\u8bc1\u5b9e\u819c\u86cb\u767d\u7ed3\u6784\u7684\u6709\u529b\u5de5\u5177\u3002\u672c\u9879\u76ee\u62df\u91c7\u7528\u56fa\u4f53\u6838\u78c1\u5171\u632f\u6280\u672f\u5728\u5927\u80a0\u6746\u83cc\u78f7\u8102\u819c\u7684\u73af\u5883\u4e0b\u5bf9DAGK\u7684\u4e09\u7ef4\u7ed3\u6784\u8fdb\u884c\u89e3\u6790\uff0c\u5e76\u5206\u6790\u4e0d\u540c\u73af\u5883\u4e0bDAGK\u6d3b\u6027\u533a\u57df\u7684\u7ed3\u6784\u53d8\u5316\uff0c\u9610\u91ca\u819c\u86cb\u767d\u7ed3\u6784\u4e0e\u529f\u80fd\u5bf9\u819c\u73af\u5883\u7684\u4f9d\u8d56\u6027\u3002", "\u82f1\u6587\u6458\u8981": "The structures of membrane proteins are profoundly influenced by membrane\u2013protein interactions. To date, more than 90% structures of membrane protein in the PDB have been determined in membrane mimetic environments-detergent micelles. However, it is very difficult to obtain membrane mimetic environments that support the native structure and function of a membrane protein. Escherichia coli diacylglycerol kinase (DAGK) is a very important transmembrane protein of which three dimensional structure has been determined in detergent micelles or lipid cubic phase by solution-state NMR or X-Ray crystallography. Due to the different membrane mimetic environments, the two structures differ obviously. Solid-state NMR is a powerful tool for studying structures of membrane proteins in the native-like membrane environments. This project aims to use Solid-state NMR to determin the sturcture of DAGK in Escherichia coli total lipids bilayer. Then, we will expain the influence of membrane environments on membrane protein structure and function by comparation the structures of DAGK active domain in different membrane environments.", "\u8d1f\u8d23\u4eba\u804c\u79f0": "\u52a9\u7406\u7814\u7a76\u5458"}, {"h": "", "\u9879\u76ee\u540d\u79f0": "\u4e0eALS/FTD\u76f8\u5173\u8054\u7684C9orf72\u516d\u6838\u82f7\u9178\u91cd\u590d\u6269\u589e\u5f62\u6210G-\u56db\u94fe\u4f53\u7684\u7ed3\u6784\u7814\u7a76", "\u6279\u51c6\u53f7": "31500604", "\u9879\u76ee\u7c7b\u522b": "\u9752\u5e74\u79d1\u5b66\u57fa\u91d1\u9879\u76ee", "\u4f9d\u6258\u5355\u4f4d": "\u9999\u6e2f\u79d1\u6280\u5927\u5b66\u6df1\u5733\u7814\u7a76\u9662", "\u9879\u76ee\u8d1f\u8d23\u4eba": "\u5468\u6ce2", "\u8d44\u52a9\u7ecf\u8d39(\u4e07\u5143)": "20", "\u6279\u51c6\u5e74\u5ea6": "2015", "\u5173\u952e\u8bcd": "\u6838\u78c1\u5171\u632f\uff1bG-\u56db\u94fe\u4f53\uff1bC9orf72\u516d\u6838\u82f7\u9178\u91cd\u590d\u6269\u589e\uff1b\u808c\u840e\u7f29\u6027\u4fa7\u7d22\u786c\u5316\u75c7\uff1b\u989d\u989e\u53f6\u75f4\u5446", "\u662f\u5426\u7ed3\u9898": "\u662f", "\u7814\u7a76\u6210\u679c(\u671f\u520a\u8bba\u6587;\u4f1a\u8bae\u8bba\u6587;\u8457\u4f5c;\u5956\u52b1;\u4e13\u5229)": "2;0;0;0;0", "\u4f9d\u6258\u5355\u4f4dID": "404024", "\u9879\u76ee\u8d1f\u8d23\u4ebaID": "100175543", "\u9879\u76ee\u7c7b\u522b\u4ee3\u7801": "630", "\u7533\u8bf7\u4ee3\u7801": "C050101", "\u8d77\u6b62\u5e74\u6708": "2016-01\u81f32018-12", "\u4e2d\u6587\u6458\u8981": "\u808c\u840e\u7f29\u6027\u4fa7\u7d22\u786c\u5316\u75c7\uff08ALS\uff09\u548c\u989d\u989e\u53f6\u75f4\u5446\uff08FTD\uff09\u662f\u4e25\u91cd\u7684\u795e\u7ecf\u9000\u884c\u6027\u75be\u75c5\u3002\u5728\u5bb6\u65cf\u6027\u6216\u6563\u53d1\u6027ALS/FTD\u60a3\u8005\u4e2d\uff0c\u4f4d\u4e8e9\u53f7\u67d3\u8272\u4f53\u7b2c72\u4e2a\u5f00\u653e\u9605\u8bfb\u6846\u57fa\u56e0\uff08C9orf72\uff09\u7684GGGGCC\u516d\u6838\u82f7\u9178\u91cd\u590d\u6269\u589e\uff08HRE\uff09\u662f\u6700\u5e38\u89c1\u7684\u9057\u4f20\u81f4\u75c5\u56e0\u5b50\u3002\u4ee5\u5f80\u7814\u7a76\u8868\u660e\uff0cC9orf72 HRE\u65e0\u8bba\u662f\u4f5c\u4e3aDNA\u6216\u8f6c\u5f55\u7684RNA\u4ea7\u7269\uff0c\u5747\u53ef\u6298\u53e0\u6210\u5177\u6709\u4e0d\u540c\u7ed3\u6784\u7684G-\u56db\u94fe\u4f53\uff0c\u5e76\u4e0eALS/FTD\u7684\u81f4\u75c5\u673a\u7406\u5bc6\u5207\u76f8\u5173\u3002\u7531\u4e8e\u7f3a\u4e4f\u76f8\u5173G-\u56db\u94fe\u4f53\u7684\u9ad8\u5206\u8fa8\u7387\u7ed3\u6784\u4fe1\u606f\uff0cC9orf72 HRE\u5f62\u6210G-\u56db\u94fe\u4f53\u7684\u5206\u5b50\u673a\u7406\u4ecd\u4e0d\u6e05\u695a\u3002\u672c\u7814\u7a76\u5c06\u5229\u7528\u6838\u78c1\u5171\u632f\u6280\u672f\u9996\u6b21\u83b7\u53d6C9orf72 HRE DNA\u53caRNA G-\u56db\u94fe\u4f53\u7684\u9ad8\u5206\u8fa8\u7387\u7ed3\u6784\uff0c\u5bf9\u4e8e\u5728ALS/FTD\u60a3\u8005\u4e2d\u7531\u4e8e\u6b64\u79cd\u7ed3\u6784\u5bfc\u81f4\u7684\u5f02\u5e38\u8f6c\u5f55\u4ea7\u7269\u8bf1\u53d1\u75be\u75c5\u7684\u5206\u5b50\u673a\u7406\u63d0\u4f9b\u6781\u6709\u4ef7\u503c\u7684\u4fe1\u606f\uff0c\u5e76\u4e14\u4e3a\u9488\u5bf9C9orf72 HRE G-\u56db\u94fe\u4f53\u8bbe\u8ba1\u5c0f\u5206\u5b50\u7528\u4ee5\u9776\u5411\u8c03\u8282ALS/ FTD\u7684\u53d1\u75c5\u673a\u5236\u5960\u5b9a\u5fc5\u8981\u7684\u7ed3\u6784\u5b66\u57fa\u7840\u3002", "\u82f1\u6587\u6458\u8981": "Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are devastating neurological diseases. Abnormal expansion of a hexanucleotide repeat, (GGGGCC)n, is the most common genetic cause of familial and sporadic forms of ALS and FTD. This nucleotide repeat element is located in a non-protein-coding region of the C9orf72 gene. Previous studies suggested that the C9orf72 hexanucleotide repeat expansion (HRE), either as DNA or the transcribed RNA, can fold into G-quadruplexes with distinct structures. It could also form transcriptionally induced RNA-DNA hybrids known as R-loops. These structural polymorphisms lead to C9orf72 HRE-containing abortive transcripts, which may aggregate and form RNA foci in patient cells. Despite the critical connection of C9orf72 HRE G-quadruplexes to the pathogenic mechanism of C9orf72 HRE-linked ALS/FTD, the molecular basis of G-quadruplex formation by C9orf72 HRE remains elusive..In this project, we plan to perform systematic biochemical and structural characterizations for C9orf72 HRE G-quadruplexes. First, we will determine the 3D structure of G-quadruplex formed by the C9orf72 HRE DNA. In our preliminary study, we successfully obtained a homogenous DNA sample, d(GGGGCC)4, which favored a monomeric G-quadruplex fold. We have determined the topology of this G-quadruplex DNA using the nuclear magnetic resonance (NMR) approach. It forms a chair-type G-quadruplex with a four-layer antiparallel G-tetra core and three edgewise loops, which is distinct from known structures of chair-type G-quadruplexes. We will further resolve its detailed structure using NMR techniques. We have also successfully obtained a homogeneous C9orf72 HRE RNA sample with sufficient quality for NMR structure determination. Unlike the monomeric d(GGGGCC)4 DNA, this RNA, r(GGGGCC)GGGG, is an asymmetric dimer. We will perform more NMR studies to obtain its 3D structure. As no structure of the C9orf72 HRE G-quadruplex has ever been solved, the structural information of C9orf72 HRE DNA/RNA G-quadruplexes to be obtained in the current project will provide valuable insights into the molecular mechanism of abortive transcripts formation by C9orf72 HRE and RNA foci appearance in ALS/FTD patients. The outcome of the proposed research will not only provide insight into the molecular mechanism underlying the C9orf72 HRE G-quadruplex formation in the etiology of ALS/FTD, but may also lay the necessary basis for designing small molecules that therapeutically target C9orf72 HRE G-quadruplexes for the modulation of ALS/FTD pathogenesis.", "\u8d1f\u8d23\u4eba\u804c\u79f0": "\u526f\u7814\u7a76\u5458"}, {"h": "", "\u9879\u76ee\u540d\u79f0": "Sema-Plexin\u4fe1\u53f7\u901a\u8def\u4e2dFARP2\u7684\u7ed3\u6784\u4e0e\u529f\u80fd\u7814\u7a76", "\u6279\u51c6\u53f7": "31500605", "\u9879\u76ee\u7c7b\u522b": "\u9752\u5e74\u79d1\u5b66\u57fa\u91d1\u9879\u76ee", "\u4f9d\u6258\u5355\u4f4d": "\u534e\u4e2d\u79d1\u6280\u5927\u5b66", "\u9879\u76ee\u8d1f\u8d23\u4eba": "\u8d3a\u6653\u9759", "\u8d44\u52a9\u7ecf\u8d39(\u4e07\u5143)": "21", "\u6279\u51c6\u5e74\u5ea6": "2015", "\u5173\u952e\u8bcd": "\u86cb\u767d\u8d28\u7ed3\u6784\uff1b\u76f8\u4e92\u4f5c\u7528\uff1b\u8f74\u7a81\u5bfc\u5411", "\u662f\u5426\u7ed3\u9898": "\u662f", "\u7814\u7a76\u6210\u679c(\u671f\u520a\u8bba\u6587;\u4f1a\u8bae\u8bba\u6587;\u8457\u4f5c;\u5956\u52b1;\u4e13\u5229)": "2;0;0;0;0", "\u4f9d\u6258\u5355\u4f4dID": "100113", "\u9879\u76ee\u8d1f\u8d23\u4ebaID": "100154722", "\u9879\u76ee\u7c7b\u522b\u4ee3\u7801": "630", "\u7533\u8bf7\u4ee3\u7801": "C050101", "\u8d77\u6b62\u5e74\u6708": "2016-01\u81f32018-12", "\u4e2d\u6587\u6458\u8981": "\u795e\u7ecf\u7cfb\u7edf\u7684\u7cbe\u786e\u53d1\u80b2\u53d1\u5c55\u79bb\u4e0d\u5f00\u8f74\u7a81\u5bfc\u5411\u3002\u795e\u7ecf\u7ec6\u80de\u751f\u957f\u690e\u4e0a\u7684\u53d7\u4f53\u63a5\u53d7\u73af\u5883\u4e2d\u7684\u8f74\u7a81\u5bfc\u5411\u56e0\u5b50\u4f20\u9012\u7684\u4fe1\u53f7\uff0c\u7ecf\u8fc7\u4e00\u7cfb\u5217\u86cb\u767d\u7684\u4f20\u9012\uff0c\u6700\u540e\u4f5c\u7528\u4e8e\u7ec6\u80de\u9aa8\u67b6\u86cb\u767d\uff0c\u4ece\u800c\u5f71\u54cd\u751f\u957f\u690e\u7684\u8d70\u5411\u3002Semaphorin-Plexin \u901a\u8def\u662f\u5176\u4e2d\u91cd\u8981\u7684\u4fe1\u53f7\u901a\u8def\u4e4b\u4e00\uff0c\u6211\u4eec\u7684\u7814\u7a76\u91cd\u70b9\u662f\u8fd9\u4e00\u901a\u8def\u4e2dplexin\u7684\u4e0b\u6e38\u4e92\u4f5c\u86cb\u767dFARP2\u3002FARP2 N\u7aef\u7684FERM\u7ed3\u6784\u57df\u4ecb\u5bfc\u5b83\u4e0ePlexin\u4e4b\u95f4\u7684\u76f8\u4e92\u4f5c\u7528\uff0c\u4f46\u662f\u4e8c\u8005\u4e4b\u95f4\u7684\u4e92\u4f5c\u6a21\u5f0f\u4e0e\u5206\u5b50\u673a\u5236\u8fd8\u4e0d\u6e05\u695a\u3002\u672c\u9879\u76ee\u5c06\u5229\u7528\u6676\u4f53\u751f\u7269\u5b66\uff0c\u751f\u7269\u5316\u5b66\uff0c\u7ec6\u80de\u751f\u7269\u5b66\u7b49\u624b\u6bb5\uff0c\u5728\u7ed3\u6784\u4e0e\u529f\u80fd\u4e0a\u7814\u7a76FARP2\u53ca\u5176\u4e0ePlexin\u7684\u4e92\u4f5c\u5173\u7cfb\u548c\u5206\u5b50\u8c03\u63a7\u673a\u5236\uff0c\u4e3a\u8fdb\u4e00\u6b65\u7406\u89e3Sema-Plexin\u901a\u8def\u4e0b\u6e38\u4fe1\u53f7\u4f20\u5bfc\u673a\u5236\u63d0\u4f9b\u5206\u5b50\u4f9d\u636e\u3002\u6211\u4eec\u4e4b\u524d\u7684\u7ed3\u6784\u751f\u7269\u5b66\u7814\u7a76\u53d1\u73b0FARP2 \u7684DH-PH-PH\u7ed3\u6784\u57df\u662f\u4e00\u79cd\u4ee5\u81ea\u6211\u6291\u5236\u6784\u8c61\u5b58\u5728\u7684\u5c0fGTP\u9176\u7684\u9e1f\u6838\u82f7\u9178\u4ea4\u6362\u56e0\u5b50(GEF)\uff0c\u672c\u9879\u76ee\u5c06\u8fdb\u4e00\u6b65\u63a2\u8ba8\u5982\u4f55\u6fc0\u6d3bFARP2\u7684GEF\u6d3b\u6027\u3002", "\u82f1\u6587\u6458\u8981": "\u82f1\u6587\u6458\u8981.The correct wiring of the nervous system relies on the precise axon guidance. During development of the nervous system, axons are guided to their proper targets by sensing a variety of extracellular cues in the local environment. The receptor protein on the neuronal growth cones which is located at the tip of the growing axon, recognizes guidance cues. The signal finally selectively alters the stability of the actin cytoskeleton and microtubules that determine the rate and direction  of   axon  extension.  Semaphorin-Plexin  is  one  of  the  classic ligand/receptor systems involved in this process\uff0c and we will focus on FARP2, which is a downstream partner of Plexin A1. FARP2 interacts with Plexin A1 though its N terminal FERM domain, but how they bind is still not clear. We are using  the  combination  of  protein  X-ray  crystallography,  biochemical techniques and cell based assay to study the structure and function of FARP2 and its interaction and regulation with Plexin A1. Our research will help us to understand the molecular regulation mechanisms of downstream signal transduction of Sema-plexin pathway.  C terminal domain DH-PH-PH of FARP2 is an auto-inhibited Guanine nucleotide exchange factor (GEF) based on our previous studies, and we will study how to active GEF activity further.", "\u8d1f\u8d23\u4eba\u804c\u79f0": "\u6559\u6388"}, {"h": "", "\u9879\u76ee\u540d\u79f0": "Tip49a/Tip49b\u53ca\u5176\u76f8\u5173\u590d\u5408\u7269\u7684\u51b7\u51bb\u7535\u955c\u7ed3\u6784\u7814\u7a76", "\u6279\u51c6\u53f7": "31500606", "\u9879\u76ee\u7c7b\u522b": "\u9752\u5e74\u79d1\u5b66\u57fa\u91d1\u9879\u76ee", "\u4f9d\u6258\u5355\u4f4d": "\u5fb7\u5dde\u5b66\u9662", "\u9879\u76ee\u8d1f\u8d23\u4eba": "\u5b8b\u5cf0", "\u8d44\u52a9\u7ecf\u8d39(\u4e07\u5143)": "20", "\u6279\u51c6\u5e74\u5ea6": "2015", "\u5173\u952e\u8bcd": "\u51b7\u51bb\u7535\u955c\uff1b\u5355\u9897\u7c92\u4e09\u7ef4\u91cd\u6784\uff1b\u86cb\u767d\u590d\u5408\u7269\u7ec4\u88c5", "\u662f\u5426\u7ed3\u9898": "\u662f", "\u7814\u7a76\u6210\u679c(\u671f\u520a\u8bba\u6587;\u4f1a\u8bae\u8bba\u6587;\u8457\u4f5c;\u5956\u52b1;\u4e13\u5229)": "4;0;0;0;0", "\u4f9d\u6258\u5355\u4f4dID": "400969", "\u9879\u76ee\u8d1f\u8d23\u4ebaID": "100181269", "\u9879\u76ee\u7c7b\u522b\u4ee3\u7801": "630", "\u7533\u8bf7\u4ee3\u7801": "C050101", "\u8d77\u6b62\u5e74\u6708": "2016-01\u81f32018-12", "\u4e2d\u6587\u6458\u8981": "Tip49a\u548cTip49b\u662fAAA+\u8d85\u5bb6\u65cf\u7684\u4e24\u4e2a\u86cb\u767d\uff0c\u5b83\u4eec\u4fdd\u5b88\u5730\u5b58\u5728\u4e8e\u4ece\u9175\u6bcd\u5230\u4eba\u7684\u591a\u4e2a\u7269\u79cd\u4e2d\uff0c\u5728\u7ec6\u80de\u5185\u901a\u5e38\u4ee5\u590d\u5408\u7269\u7684\u5f62\u5f0f\u5b58\u5728\u3002\u5b83\u4eec\u5728DNA\u635f\u4f24\u4fee\u590d\u3001\u8f6c\u5f55\u8c03\u63a7\u3001snoRNP\u6210\u719f\u3001\u67d3\u8272\u8d28\u91cd\u5851\u7b49\u751f\u547d\u6d3b\u52a8\u4e2d\u53d1\u6325\u91cd\u8981\u7684\u8c03\u63a7\u4f5c\u7528\uff0c\u4f46\u8fc4\u4eca\u4e3a\u6b62\u4ecd\u7136\u6ca1\u6709Tip49a/Tip49b\u5168\u957f\u86cb\u767d\u76f8\u5173\u590d\u5408\u7269\u7684\u7ed3\u6784\u62a5\u9053\u3002\u672c\u7814\u7a76\u62df\u4e3b\u8981\u5e94\u7528\u51b7\u51bb\u7535\u955c\u5355\u9897\u7c92\u4e09\u7ef4\u91cd\u6784\u6280\u672f\u89e3\u6790\u4eba\u6e90Tip49a/Tip49b\u53ca\u5176\u53c2\u4e0e\u5f62\u6210\u7684\u4e24\u79cd\u9ad8\u7ea7\u590d\u5408\u7269\uff08R2TP\u3001Tip49a/Tip49b-\u6838\u5c0f\u4f53\uff09\u7684\u9ad8\u7cbe\u5ea6\u4e09\u7ef4\u7ed3\u6784\uff0c\u5e76\u7ed3\u5408\u751f\u5316\u5b9e\u9a8c\u786e\u5b9aTip49a/Tip49b\u5728\u4e24\u79cd\u9ad8\u7ea7\u590d\u5408\u7269\u4e2d\u7684\u4f5c\u7528\u3002\u672c\u9879\u76ee\u7684\u7814\u7a76\u6210\u679c\u5c06\u4e3a\u7406\u89e3Tip49a/Tip49b\u5728snoRNP\u7ec4\u88c5\uff08R2TP\u590d\u5408\u7269\uff09\u548cATP\u4f9d\u8d56\u7684\u67d3\u8272\u8d28\u91cd\u5851\uff08Tip49a/Tip49b-\u6838\u5c0f\u4f53\u590d\u5408\u7269\uff09\u4e2d\u7684\u5de5\u4f5c\u673a\u5236\u63d0\u4f9b\u53ef\u9760\u7684\u7ed3\u6784\u4fe1\u606f\u3002", "\u82f1\u6587\u6458\u8981": "Tip49a and Tip49b are two structurally and functionally highly related proteins that belong to the AAA+ (ATPase Associated with diverse cellular Activities) superfamily. They are existed in many species of which ranging from yeast to human. Both Tip49a and Tip49b are conserved components of various multi-subunit complexes, which are linked to a wide range of cellular processes, such as DNA damage response, transcription regulation, snoRNP biogenesis and ATP-dependent chromatin remodeling. Despite their diverse roles, there is no available high resolution structure of full-length Tip49a/Tip49b protein complex. The mainly purpose of our research is to reveal the high resolution structures of dodecameric Tip49a/Tip49b and determine their functions in two larger complexes which containing them, R2TP and Tip49a/Tip49b-nucleosome complex, by using cryo-EM single particle analysis combining with biochemical and biophysical techniques. Our research will provide insights into the structural basis of Tip49a/Tip49b in mediating snoRNP biogenesis(R2TP complex) and ATP-dependent chromatin remodeling(Tip49a/Tip49b-nucleosome complex).", "\u8d1f\u8d23\u4eba\u804c\u79f0": "\u6559\u6388"}, {"h": "", "\u9879\u76ee\u540d\u79f0": "\u7ed3\u6838\u5206\u679d\u6746\u83cc\u5206\u679d\u83cc\u9178\u5408\u6210\u9014\u5f84\u8131\u6c34\u9176HadABC\u590d\u5408\u7269\u4e0e\u591a\u79cd\u6297\u7ed3\u6838\u6291\u5236\u5242\u7684\u7ed3\u6784\u548c\u529f\u80fd\u7814\u7a76", "\u6279\u51c6\u53f7": "31500607", "\u9879\u76ee\u7c7b\u522b": "\u9752\u5e74\u79d1\u5b66\u57fa\u91d1\u9879\u76ee", "\u4f9d\u6258\u5355\u4f4d": "\u4e2d\u56fd\u79d1\u5b66\u9662\u4e0a\u6d77\u751f\u547d\u79d1\u5b66\u7814\u7a76\u9662", "\u9879\u76ee\u8d1f\u8d23\u4eba": "\u674e\u4fca", "\u8d44\u52a9\u7ecf\u8d39(\u4e07\u5143)": "20", "\u6279\u51c6\u5e74\u5ea6": "2015", "\u5173\u952e\u8bcd": "\u7ed3\u6838\u5206\u679d\u6746\u83cc\uff1b\u6676\u4f53\u7ed3\u6784\uff1b\u5206\u679d\u83cc\u9178\uff1b\u8131\u6c34\u9176\uff1b\u836f\u7269\u9776\u70b9", "\u662f\u5426\u7ed3\u9898": "\u662f", "\u7814\u7a76\u6210\u679c(\u671f\u520a\u8bba\u6587;\u4f1a\u8bae\u8bba\u6587;\u8457\u4f5c;\u5956\u52b1;\u4e13\u5229)": "3;0;0;0;0", "\u4f9d\u6258\u5355\u4f4dID": "201022", "\u9879\u76ee\u8d1f\u8d23\u4ebaID": "100175031", "\u9879\u76ee\u7c7b\u522b\u4ee3\u7801": "630", "\u7533\u8bf7\u4ee3\u7801": "C050101", "\u8d77\u6b62\u5e74\u6708": "2016-01\u81f32018-12", "\u4e2d\u6587\u6458\u8981": "\u7ed3\u6838\u75c5\u662f\u76ee\u524d\u4e16\u754c\u4e0a\u81f4\u6b7b\u7387\u6700\u9ad8\u3001\u4f20\u64ad\u8303\u56f4\u6700\u5e7f\u7684\u7ec6\u83cc\u6027\u75be\u75c5\u3002\u7ed3\u6838\u5206\u679d\u6746\u83cc\u662f\u5f15\u53d1\u7ed3\u6838\u75c5\u7684\u75c5\u539f\u83cc\uff0c\u7531\u4e8e\u8010\u591a\u836f\u83cc\u682a\uff08MDR-TB\uff09\u548c\u5e7f\u6cdb\u8010\u836f\u83cc\u682a\uff08XDR-TB\uff09\u7684\u51fa\u73b0\uff0c\u4f7f\u5f97\u73b0\u6709\u836f\u7269\u7684\u6cbb\u7597\u51e0\u4e4e\u5931\u6548\u3002\u56e0\u6b64\uff0c\u5bfb\u627e\u65b0\u7684\u836f\u7269\u9776\u70b9\u4ee5\u53ca\u7814\u7a76\u5168\u65b0\u4f5c\u7528\u673a\u5236\u7684\u5f3a\u529b\u6297\u7ed3\u6838\u836f\u7269\u5df2\u7ecf\u6210\u4e3a\u8feb\u5728\u7709\u776b\u7684\u91cd\u8981\u4efb\u52a1\u3002\u7531\u81f4\u5bc6\u7684\u5206\u679d\u83cc\u9178\u5c42\u6784\u6210\u7684\u7ec6\u80de\u58c1\u4f7f\u5f97\u7ed3\u6838\u5206\u679d\u6746\u83cc\u53ef\u4ee5\u9003\u907f\u514d\u75ab\u653b\u51fb\u548c\u6709\u5bb3\u7269\u8d28\u5165\u4fb5\u4ece\u800c\u80fd\u591f\u5b58\u6d3b\u3002\u8131\u6c22\u9176HadAB\u548cHadBC\u662fII\u578b\u5206\u679d\u83cc\u9178\u8102\u94fe\u5ef6\u4f38\u7cfb\u7edf\uff08FAS-II\uff09\u4e2d\u6700\u665a\u88ab\u53d1\u73b0\u7684\u4e24\u5bf9\u590d\u5408\u7269\uff0c\u4e5f\u662f\u4e00\u7ebf\u836f\u7269\u5f02\u70df\u80bc\u9776\u70b9InhA\u7684\u4e0b\u6e38\u86cb\u767d\u3002\u8fc4\u4eca\u4e3a\u6b62\uff0c\u5176\u4e09\u7ef4\u7ed3\u6784\u548c\u50ac\u5316\u673a\u5236\u5c1a\u4e0d\u6e05\u695a\u3002\u672c\u7814\u7a76\u9879\u76ee\u53ef\u4ee5\u586b\u8865\u8fd9\u65b9\u9762\u7684\u7a7a\u767d\uff0c\u4ece\u5206\u5b50\u6c34\u5e73\u4e0a\u63a8\u8fdb\u5176\u9176\u6d3b\u673a\u5236\u7684\u7814\u7a76\uff1b\u800cHadABC\u4e0e\u9ec4\u916e\u7c7b\u6291\u5236\u5242\u548c\u6297\u7ed3\u6838\u836f\u7269Isoxyl\u3001Thiacetazone\u590d\u5408\u7269\u7ed3\u6784\u7814\u7a76\u5c06\u63ed\u793a\u5176\u6297\u7ed3\u6838\u7684\u6291\u5236\u673a\u5236\uff0c\u5bf9\u57fa\u4e8eHadABC\u7684\u6297\u7ed3\u6838\u836f\u7269\u5f00\u53d1\u63d0\u4f9b\u91cd\u8981\u7ebf\u7d22\u548c\u53ef\u9760\u7684\u7ed3\u6784\u751f\u7269\u5b66\u57fa\u7840\u3002", "\u82f1\u6587\u6458\u8981": "Tuberculosis (TB) is the most lethal and widely spread bacterial infectious disease over the world, mainly caused by the pathogenic Mycobacterium tuberculosis (Mtb). Seriously, the emergence of Multi-drug resistant TB (MDR-TB) and extensively drug resistant TB (XDR-TB) make currently used drugs ineffective to cure TB. Therefore, developing novel and effective anti-TB drugs following research of newly found drug targets has already been an urgent and important mission now. Mtb is hard to kill under host immune attack and survives from toxicant invasion because of the dense and hydrophobic mycolic acid layer of cell wall. Both of HadAB and HadBC were the dehydratases, which were the last and latest identified piece of the type II fatty acid synthesis (FAS-II) system, involved in the elongation of mycolic acid chain. The importance of mycolic acid for Mtb makes all the enzymes in this synthesis pathway potential drug targets including HadAB and HadBC. In fact, they were exact downstream enzymes of InhA, an approved target of currently first-line drug isoniazid. So far as we know, there are no crystal structures of HadAB and HadBC reported and the knowledge of catalytic mechanism is unclear as well. Thus, our research will fill in these gaps by deepening our understanding of it enzymatic catalysis from molecular perspective. Our research also aims to unveil inhibition mechanisms by studying the complex structures of HadABC with either flavonoid inhibitors or anti-TB drugs Isoxyl and Thiacetazone, which will lay sound structural basis and provide important clues for the anti-TB drug development.", "\u8d1f\u8d23\u4eba\u804c\u79f0": "\u526f\u7814\u7a76\u5458"}, {"h": "", "\u9879\u76ee\u540d\u79f0": "\u5355\u9897\u7c92\u4f4e\u6e29\u900f\u5c04\u7535\u955c\u9ad8\u5206\u8fa8\u7387\u6570\u636e\u6536\u96c6\u7528\u652f\u6301\u819c\u7684\u7814\u7a76", "\u6279\u51c6\u53f7": "31500608", "\u9879\u76ee\u7c7b\u522b": "\u9752\u5e74\u79d1\u5b66\u57fa\u91d1\u9879\u76ee", "\u4f9d\u6258\u5355\u4f4d": "\u4e2d\u56fd\u79d1\u5b66\u9662\u751f\u7269\u7269\u7406\u7814\u7a76\u6240", "\u9879\u76ee\u8d1f\u8d23\u4eba": "\u9ec4\u5c0f\u4fca", "\u8d44\u52a9\u7ecf\u8d39(\u4e07\u5143)": "20", "\u6279\u51c6\u5e74\u5ea6": "2015", "\u5173\u952e\u8bcd": "\u51b7\u51bb\u7535\u955c\u6210\u50cf\u6280\u672f\uff1b\u5355\u9897\u7c92\u4e09\u7ef4\u91cd\u6784\uff1b\u5355\u9897\u7c92\u51b7\u51bb\u7535\u955c\u6cd5", "\u662f\u5426\u7ed3\u9898": "\u662f", "\u7814\u7a76\u6210\u679c(\u671f\u520a\u8bba\u6587;\u4f1a\u8bae\u8bba\u6587;\u8457\u4f5c;\u5956\u52b1;\u4e13\u5229)": "0;0;0;0;2", "\u4f9d\u6258\u5355\u4f4dID": "100067", "\u9879\u76ee\u8d1f\u8d23\u4ebaID": "100172851", "\u9879\u76ee\u7c7b\u522b\u4ee3\u7801": "630", "\u7533\u8bf7\u4ee3\u7801": "C050101", "\u8d77\u6b62\u5e74\u6708": "2016-01\u81f32018-12", "\u4e2d\u6587\u6458\u8981": "\u5355\u9897\u7c92\u4f4e\u6e29\u900f\u5c04\u7535\u955c\u6280\u672f\u53d1\u5c55\u81f3\u4eca\uff0c\u6700\u5927\u7684\u74f6\u9888\u5728\u4e8e\u6837\u54c1\u5236\u5907\u3002\u800c\u6837\u54c1\u5236\u5907\u4e0d\u53ef\u6216\u7f3a\u7684\u8017\u6750\u662f\u900f\u5c04\u7535\u955c\u8f7d\u7f51\u3002\u900f\u5c04\u7535\u955c\u8f7d\u7f51\uff08\u7279\u522b\u662f\u8986\u5728\u5176\u4e0a\u7684\u652f\u6301\u819c\uff09\u7684\u4eb2\u6c34\u6027\u80fd\uff0c\u673a\u68b0\u6027\u80fd\uff0c\u5bfc\u7535\u6027\u80fd\u7b49\u76f4\u63a5\u5f71\u54cd\u7740\u5236\u5907\u6837\u54c1\u7684\u8d28\u91cf\u53ca\u6570\u636e\u6536\u96c6\u6548\u7387\u3002\u672c\u9879\u76ee\u5728\u5df2\u81ea\u4e3b\u7814\u5236\u5e76\u5e94\u7528\u7684GIG\u5fae\u9635\u5217\u78b3\u652f\u6301\u819c\u7684\u57fa\u7840\u4e0a\uff0c\u7ee7\u7eed\u7814\u53d1\u66f4\u7b26\u5408\u5b9e\u9645\u9700\u8981\u7684\u7279\u5b9a\u539a\u5ea6\u3001\u5b54\u5f84\u53ca\u5b54\u95f4\u8ddd\u7684\u5fae\u9635\u5217\u652f\u6301\u819c\uff0c\u5e76\u4ee5\u63d0\u5347\u652f\u6301\u819c\u7684\u5bfc\u7535\u6027\u4e3a\u76ee\u6807\u4ee5\u5f00\u53d1\u51fa\u7b2c\u4e8c\u4ee3\u7684\u8be5\u7cfb\u5217\u5fae\u9635\u5217\u652f\u6301\u819c\u3002\u6700\u7ec8\u5c06\u7b2c\u4e8c\u4ee3\u7684\u5fae\u9635\u5217\u652f\u6301\u819c\u5e94\u7528\u5230\u4f4e\u6e29\u900f\u5c04\u7535\u955c\u6280\u672f\u4e2d\uff0c\u964d\u4f4e\u7535\u5b50\u675f\u5f15\u53d1\u7684\u56fe\u50cf\u6f02\u79fb\u72b6\u51b5\uff0c\u63d0\u5347\u5355\u9897\u7c92\u4f4e\u6e29\u900f\u5c04\u7535\u955c\u6210\u50cf\u8d28\u91cf\u548c\u6570\u636e\u6536\u96c6\u6548\u7387\u3002", "\u82f1\u6587\u6458\u8981": "Single particle cryo electron microscopy develops very fast these years. The bottle neck of this technique is at sample preparation. Among all those important factors of sample preparation, e.g. protein purity, concentration, rigidity et al., the properties of TEM grid, to be specific, the properties of supporting film on the TEM grid, is essential to preparing a good cryo sample. Hydrophilicity, strong mechanical strength, high conductivity of the supporting film affect the quality of prepared cryo sample and the efficiency of data collection. Based on the self-developed amorphous carbon film with fixed-pattern micro array (brand name GIG), this study aims to develop more suitable supporting films for cryoTEM usage. It includes designing suitable film thickness, hole size, spacing between hole which leads to high efficiency data collection, and increasing the conductivity of the supporting film at liquid nitrogen temperature which reduces the beam induce movement and enhances the quality of cryoEM images.", "\u8d1f\u8d23\u4eba\u804c\u79f0": "\u9ad8\u7ea7\u5de5\u7a0b\u5e08"}, {"h": "", "\u9879\u76ee\u540d\u79f0": "\u5e72\u6270\u7d20\u8bf1\u5bfc\u86cb\u767dIFIT/ISG56\u5bb6\u65cf\u6297\u75c5\u6bd2\u529f\u80fd\u7684\u7ed3\u6784\u751f\u7269\u5b66\u7814\u7a76", "\u6279\u51c6\u53f7": "31500609", "\u9879\u76ee\u7c7b\u522b": "\u9752\u5e74\u79d1\u5b66\u57fa\u91d1\u9879\u76ee", "\u4f9d\u6258\u5355\u4f4d": "\u4e2d\u56fd\u79d1\u5b66\u9662\u751f\u7269\u7269\u7406\u7814\u7a76\u6240", "\u9879\u76ee\u8d1f\u8d23\u4eba": "\u51af\u5cf0", "\u8d44\u52a9\u7ecf\u8d39(\u4e07\u5143)": "20", "\u6279\u51c6\u5e74\u5ea6": "2015", "\u5173\u952e\u8bcd": "IFIT/ISG56\u5bb6\u65cf\u86cb\u767d\uff1b\u6297\u75c5\u6bd2\uff1b\u5929\u7136\u514d\u75ab", "\u662f\u5426\u7ed3\u9898": "\u662f", "\u7814\u7a76\u6210\u679c(\u671f\u520a\u8bba\u6587;\u4f1a\u8bae\u8bba\u6587;\u8457\u4f5c;\u5956\u52b1;\u4e13\u5229)": "1;0;0;0;0", "\u4f9d\u6258\u5355\u4f4dID": "100067", "\u9879\u76ee\u8d1f\u8d23\u4ebaID": "100218232", "\u9879\u76ee\u7c7b\u522b\u4ee3\u7801": "630", "\u7533\u8bf7\u4ee3\u7801": "C050101", "\u8d77\u6b62\u5e74\u6708": "2016-01\u81f32018-12", "\u4e2d\u6587\u6458\u8981": "\u75c5\u539f\u4f53\u548c\u5e72\u6270\u7d20\u80fd\u591f\u8bf1\u5bfcISG56/IFIT \u5bb6\u65cf\u86cb\u767d\u7684\u8868\u8fbe, \u5b83\u4eec\u4e0d\u4ec5\u5177\u6709\u6297\u75c5\u6bd2\u4f5c\u7528\uff0c\u800c\u4e14\u8fd8\u53c2\u4e0e\u8c03\u8282\u7ec6\u80de\u7684\u514d\u75ab\u53cd\u5e94\u3002\u524d\u671f\u6211\u4eec\u5728\u56fd\u9645\u4e0a\u7387\u5148\u89e3\u6790\u4e86\u8be5\u5bb6\u65cf\u6210\u5458\u7684\u6676\u4f53\u7ed3\u6784\uff0c\u5e76\u4e14\u901a\u8fc7\u7ed3\u6784\u4fe1\u606f\u8bc1\u5b9e\u4e86\u5176\u6297\u75c5\u6bd2\u529f\u80fd\u4e0e\u6838\u9178\u7ed3\u5408\u80fd\u529b\u6709\u5173\uff0c\u4f46\u662f\u5176\u80cc\u540e\u7684\u5206\u5b50\u673a\u5236\u5c1a\u4e0d\u660e\u786e\u3002\u672c\u9879\u76ee\u62df\u901a\u8fc7\u7ed3\u6784\u751f\u7269\u5b66\u7ed3\u5408\u7ec6\u80de\u751f\u7269\u5b66\u7684\u624b\u6bb5\uff0c\u5728\u5df2\u83b7\u5f97\u7684\u7814\u7a76\u7ed3\u679c\u57fa\u7840\u4e0a\u7cfb\u7edf\u5730\u5f00\u5c55ISG56/IFIT \u5bb6\u65cf\u5404\u4e2a\u6210\u5458\u7684\u6297\u75c5\u6bd2\u548c\u514d\u75ab\u529f\u80fd\u7684\u5206\u5b50\u673a\u5236\u7684\u7814\u7a76\uff0c\u5305\u62ec\u6bd4\u8f83\u5bb6\u65cf\u6210\u5458\u4e4b\u95f4\u7684\u6676\u4f53\u7ed3\u6784\u5dee\u5f02\uff1b\u660e\u786e\u8bc6\u522b\u548c\u7ed3\u5408\u6838\u9178\u7684\u5e8f\u5217\u548c\u7ed3\u6784\u7684\u7279\u5f02\u6027\uff1b\u68c0\u6d4b\u5728\u514d\u75ab\u53cd\u5e94\u4fe1\u53f7\u901a\u8def\u4e2d\u76f8\u4e92\u4f5c\u7528\u7684\u5206\u5b50\uff0c\u6700\u7ec8\u63ed\u793a\u5bb6\u65cf\u5404\u6210\u5458\u9009\u62e9\u6027\u6fc0\u6d3b\u8868\u8fbe\u7684\u6761\u4ef6\u548c\u7279\u5f02\u6027\u6297\u75c5\u6bd2\u7684\u539f\u56e0\u3002\u672c\u9879\u76ee\u7684\u7814\u7a76\u6210\u679c\u5c06\u5bf9\u5bbf\u4e3b\u6297\u75c5\u6bd2\u5929\u7136\u514d\u75ab\u9886\u57df\u7684\u7814\u7a76\u4ee5\u53ca\u76f8\u5e94\u7684\u514d\u75ab\u4e34\u5e8a\u6cbb\u7597\u5177\u6709\u91cd\u8981\u7684\u7406\u8bba\u548c\u73b0\u5b9e\u610f\u4e49\u3002", "\u82f1\u6587\u6458\u8981": "ISG56/IFIT family proteins\uff0cwhich be induced by interferon and pathogen\uff0chave antiviral functions and can regulate cellular immune response. Previously, we first solved the crystal structure of ISG56/IFIT family proteins and discovered that their antiviral functions are related to their ability to recognize nucleotides. However, the molecular mechanism remains unknown. In this project, we aim to reveal the mechanism of ISG56/IFIT proteins using structural and cellular biology methods. Base on the information on crystal structure differences, nucleic acid recognitions, binding partners in innate immune pathway, we try to propose the mechanism of specificity of ISG56/IFIT family proteins' antiviral functions. Our results will deepen people's understanding on innate immune response and provide practical significance on clinical treatment.", "\u8d1f\u8d23\u4eba\u804c\u79f0": "\u535a\u58eb\u540e"}, {"h": "", "\u9879\u76ee\u540d\u79f0": "Wnt\u4fe1\u53f7\u901a\u8def\u4e2d\u03b2-catenin\u53ca\u5176\u7ec6\u80de\u6838\u5185\u5171\u6fc0\u6d3b\u56e0\u5b50\u590d\u5408\u7269\u7684\u7ed3\u6784\u751f\u7269\u5b66\u7814\u7a76", "\u6279\u51c6\u53f7": "31500610", "\u9879\u76ee\u7c7b\u522b": "\u9752\u5e74\u79d1\u5b66\u57fa\u91d1\u9879\u76ee", "\u4f9d\u6258\u5355\u4f4d": "\u4e2d\u56fd\u79d1\u5b66\u9662\u751f\u7269\u7269\u7406\u7814\u7a76\u6240", "\u9879\u76ee\u8d1f\u8d23\u4eba": "\u5b59\u4f1f", "\u8d44\u52a9\u7ecf\u8d39(\u4e07\u5143)": "20", "\u6279\u51c6\u5e74\u5ea6": "2015", "\u5173\u952e\u8bcd": "\u86cb\u767d\u8d28\uff1b\u76f8\u4e92\u4f5c\u7528\uff1b\u6676\u4f53\u7b5b\u9009\uff1b\u7ed3\u6784\u89e3\u6790\uff1b\u5206\u5b50\u7f6e\u6362", "\u662f\u5426\u7ed3\u9898": "\u662f", "\u7814\u7a76\u6210\u679c(\u671f\u520a\u8bba\u6587;\u4f1a\u8bae\u8bba\u6587;\u8457\u4f5c;\u5956\u52b1;\u4e13\u5229)": "1;0;0;0;0", "\u4f9d\u6258\u5355\u4f4dID": "100067", "\u9879\u76ee\u8d1f\u8d23\u4ebaID": "100045287", "\u9879\u76ee\u7c7b\u522b\u4ee3\u7801": "630", "\u7533\u8bf7\u4ee3\u7801": "C050101", "\u8d77\u6b62\u5e74\u6708": "2016-01\u81f32018-12", "\u4e2d\u6587\u6458\u8981": "Wnt/\u03b2-catenin\u4fe1\u53f7\u901a\u8def\u7684\u8fc7\u5ea6\u6fc0\u6d3b\u4f1a\u5bfc\u81f4\u8bb8\u591a\u764c\u75c7\u7684\u53d1\u751f\u3002\u03b2-catenin\u662f\u8be5\u901a\u8def\u4e0a\u7684\u4e2d\u5fc3\u6548\u5e94\u5206\u5b50\uff0c\u5b83\u7684\u8868\u8fbe\u4e0a\u8c03\u662f\u8fd9\u4e9b\u764c\u75c7\u53d1\u751f\u7684\u9a71\u52a8\u56e0\u7d20\u3002\u5728\u7ec6\u80de\u6838\u5185\uff0c\u591a\u79cd\u5171\u6fc0\u6d3b\u56e0\u5b50\u4e0e\u03b2-catenin\u76f8\u4e92\u4f5c\u7528\uff0c\u5171\u540c\u6fc0\u6d3b\u4e0b\u6e38\u80bf\u7624\u4fc3\u8fdb\u56e0\u5b50\u5982cyclin-D\u548cc-Myc\u7684\u8f6c\u5f55\uff0c\u5176\u4e2dM1\u578b\u53c9\u5934\u6846\u86cb\u767d\uff08FoxM1\uff09\u548cPCNA\u76f8\u5173\u56e0\u5b50\uff08PAF\uff09\u5c31\u662f\u5176\u4e2d\u4e24\u4e2a\u3002FoxM1\u4fc3\u8fdb\u03b2-catenin\u5728\u7ec6\u80de\u6838\u5185\u7684\u5b9a\u4f4d\uff0c\u5e76\u53ef\u4ee5\u4fc3\u8fdbWnt\u5e94\u6fc0\u57fa\u56e0\u7684\u8868\u8fbe\uff0c\u5728\u4eba\u7c7b\u7684\u591a\u79cd\u80bf\u7624\uff08\u6bd4\u5982\u795e\u7ecf\u80f6\u8d28\u7624\uff09\u4e2d\u90fd\u6709\u8fc7\u8868\u8fbe\u3002PAF\u5219\u5728\u7ed3\u76f4\u80a0\u764c\u548c\u80a0\u5e72\u7ec6\u80de\u4e2d\u7279\u5f02\u8868\u8fbe\u3002\u56e0\u4e3a\u03b2-catenin-FoxM1\u548c\u03b2-catenin-PAF\u590d\u5408\u4f53\u7684\u5f62\u6210\u662fWnt/\u03b2-catenin\u4e0b\u6e38\u7684\u91cd\u8981\u4e8b\u4ef6\uff0c\u5bf9\u80bf\u7624\u7684\u53d1\u751f\u53ca\u6076\u5316\u8d77\u91cd\u8981\u4f5c\u7528\uff0c\u6211\u4eec\u8ba1\u5212\u5bf9\u5b83\u4eec\u5f00\u5c55\u7ed3\u6784\u751f\u7269\u5b66\u7814\u7a76\uff0c\u4ee5\u4fbf\u9610\u91ca\u76f8\u5173\u764c\u75c7\u7684\u53d1\u751f\u673a\u7406\uff0c\u5e76\u4e3a\u4eba\u7c7b\u764c\u75c7\u6cbb\u7597\u63d0\u4f9b\u65b0\u7684\u601d\u8def\u3002", "\u82f1\u6587\u6458\u8981": "Hyperactivation of the canonical Wnt/\u03b2-catenin signaling pathway can cause many types of cancers. \u03b2-catenin is the central effector of this signaling pathway, and its upregulation is a driving factor for these cancers. In the nucleus, many coactivators interact with \u03b2-catenin, activating transcription of downstream tumor-promoting factors such as cyclin-D and c-Myc. Forhead box protein M1 type (FoxM1) and PCNA-associated factor (PAF) are two \u03b2-catenin-specific transcriptional coactivators. FoxM1 promotes \u03b2-catenin nuclear localization and induces expression of Wnt responsive genes, and is overexpressed in many cancer types, including glioma. As to PAF, it is specifically expressed in colon cancer and intestine stem cells.  Because formations of \u03b2-catenin-FoxM1 and \u03b2-catenin-PAF complex are critical events downstream of Wnt/\u03b2-catenin signaling pathway, which play vital roles in tumorigenesis and metastasis of many cancers, we embark on investigating the interactions between \u03b2-catenin and FoxM1/PAF employing structural biological methods.  We aim to elucidate the molecular mechanism of tumorigenicity and try to provide novel insights into the therapy of human cancers.", "\u8d1f\u8d23\u4eba\u804c\u79f0": "\u535a\u58eb\u540e"}, {"h": "", "\u9879\u76ee\u540d\u79f0": "\u5e94\u7528\u7535\u5b50\u987a\u78c1\u5171\u632f\u6280\u672f\u63a2\u7a76\u7ed3\u6838\u5206\u679d\u6746\u83cc\u5206\u6ccc\u7cfb\u7edf\u5185\u819c\u86cb\u767dRv3882c\u8de8\u819c\u7ed3\u6784\u57df\u7684\u7ed3\u6784\u7279\u5f81", "\u6279\u51c6\u53f7": "31500611", "\u9879\u76ee\u7c7b\u522b": "\u9752\u5e74\u79d1\u5b66\u57fa\u91d1\u9879\u76ee", "\u4f9d\u6258\u5355\u4f4d": "\u4e2d\u56fd\u79d1\u5b66\u9662\u5408\u80a5\u7269\u8d28\u79d1\u5b66\u7814\u7a76\u9662", "\u9879\u76ee\u8d1f\u8d23\u4eba": "\u4e8e\u7490", "\u8d44\u52a9\u7ecf\u8d39(\u4e07\u5143)": "20", "\u6279\u51c6\u5e74\u5ea6": "2015", "\u5173\u952e\u8bcd": "\u5206\u679d\u6746\u83cc\u5206\u6ccc\u7cfb\u7edf\uff1b\u819c\u86cb\u767d\uff1b\u4f4d\u70b9\u7279\u5f02\u6027\u81ea\u65cb\u6807\u8bb0\uff1b\u7535\u5b50\u987a\u78c1\u5171\u632f\uff1b\u7ed3\u6784\u6d4b\u5b9a", "\u662f\u5426\u7ed3\u9898": "\u662f", "\u7814\u7a76\u6210\u679c(\u671f\u520a\u8bba\u6587;\u4f1a\u8bae\u8bba\u6587;\u8457\u4f5c;\u5956\u52b1;\u4e13\u5229)": "2;0;0;0;0", "\u4f9d\u6258\u5355\u4f4dID": "100212", "\u9879\u76ee\u8d1f\u8d23\u4ebaID": "100134186", "\u9879\u76ee\u7c7b\u522b\u4ee3\u7801": "630", "\u7533\u8bf7\u4ee3\u7801": "C050101", "\u8d77\u6b62\u5e74\u6708": "2016-01\u81f32018-12", "\u4e2d\u6587\u6458\u8981": "\u7ed3\u6838\u5206\u679d\u6746\u83cc\u7684ESX-1\u5206\u6ccc\u7cfb\u7edf\u80fd\u4f7f\u83cc\u4f53\u5206\u6ccc\u7684\u81f4\u75c5\u56e0\u5b50\u3001\u5b58\u6d3b\u56e0\u5b50\u7b49\u86cb\u767d\u8d28\u7a7f\u8fc7\u5176\u9ad8\u5ea6\u758f\u6c34\u81f4\u5bc6\u7684\u7ec6\u80de\u88ab\u819c\uff0c\u5bf9\u7ed3\u6838\u5206\u679d\u6746\u83cc\u7684\u6bd2\u529b\u548c\u5b58\u6d3b\u6781\u4e3a\u5173\u952e\u3002\u56e0\u6b64\uff0c\u6709\u5173ESX-1\u5206\u6ccc\u7cfb\u7edf\u76f8\u5173\u7ec4\u6210\u86cb\u767d\u7684\u7ed3\u6784\u5206\u6790\u5bf9\u4e8e\u7406\u89e3\u7ed3\u6838\u6746\u83cc\u611f\u67d3\u673a\u5236\u5177\u6709\u975e\u5e38\u91cd\u8981\u7684\u610f\u4e49\u3002Rv3882c\u86cb\u767d\u662fESX-1\u5206\u6ccc\u7cfb\u7edf\u4e2d\u4e00\u79cd\u91cd\u8981\u7684\u5185\u819c\u86cb\u767d\uff0c\u53ef\u80fd\u4e0e\u5176\u4ed6\u7ec4\u6210\u86cb\u767d\u5171\u540c\u5f62\u6210\u901a\u9053\u7c7b\u590d\u5408\u7269\uff0c\u8d1f\u8d23\u8f6c\u8fd0\u5e95\u7269\u7a7f\u8fc7\u7ec6\u80de\u88ab\u819c\uff0c\u4f46\u76ee\u524d\u5176\u7a7a\u95f4\u7ed3\u6784\u548c\u786e\u5207\u7684\u751f\u7269\u5b66\u529f\u80fd\u5c1a\u4e0d\u660e\u786e\uff0c\u4ecd\u4e9f\u5f85\u7814\u7a76\u3002\u672c\u9879\u76ee\u5c06\u7ed3\u5408\u4f4d\u70b9\u7279\u5f02\u6027\u81ea\u65cb\u6807\u8bb0\u4e0e\u7535\u5b50\u987a\u78c1\u5171\u632f\u6280\u672f\uff0c\u901a\u8fc7\u83b7\u53d6Rv3882c\u86cb\u767d\u8de8\u819c\u7ed3\u6784\u57df\u7684\u8fd0\u52a8\u6027\u4fe1\u606f\u3001\u6613\u8d8b\u6027\u4fe1\u606f\u4ee5\u53ca\u5728\u819c\u73af\u5883\u4e2d\u7684\u53d6\u5411\u4fe1\u606f\uff0c\u7efc\u5408\u5206\u6790\u5f97\u5230Rv3882c\u86cb\u767d\u8de8\u819c\u7ed3\u6784\u57df\u5728\u819c\u73af\u5883\u4e2d\u7684\u4e09\u7ef4\u7ed3\u6784\u6a21\u578b\u3002\u672c\u9879\u76ee\u7684\u987a\u5229\u5f00\u5c55\uff0c\u5c06\u4e3aRv3882c\u86cb\u767d\u7684\u7ed3\u6784\u7814\u7a76\u63d0\u4f9b\u91cd\u8981\u4f9d\u636e\uff0c\u6709\u52a9\u4e8e\u8fdb\u4e00\u6b65\u9610\u660e\u7ed3\u6838\u5206\u679d\u6746\u83cc\u7684\u5206\u6ccc\u7cfb\u7edf\u4e0e\u81f4\u75c5\u673a\u5236\uff0c\u4e5f\u4e3a\u5e94\u7528\u7535\u5b50\u987a\u78c1\u5171\u632f\u6280\u672f\u7814\u7a76\u5176\u4ed6\u819c\u86cb\u767d\u7ed3\u6784\u63d0\u4f9b\u65b9\u6cd5\u4e0e\u601d\u8def\u3002", "\u82f1\u6587\u6458\u8981": "The ESX-1 secretion system of Mycobacterium tuberculosis serves to secrete proteins, such as virulence factors and survival factors, across its highly hydrophobic and poorly permeable cell envelop, which is crucial for the virulence and survival of Mycobacterium tuberculosis. Therefore, structural investigation on component proteins of ESX-1 secretion system is very important for understanding the infection mechanisms of Mycobacterium tuberculosis. Rv0082c is a very important membrane protein of ESX-1 secretion system and is located on the inner membrane of Mycobacterium tuberculosis. It was predicted that Rv3382c forms a channel-like complex with other proteins and functions to transport the substrates across the mycobacterial cell envelope. However, the structure and function of this protein is still unclear. In this proposal, we are trying to characterize the structure of the transmembrane domain of membrane protein Rv3882c by combing Site Directed Spin Labelling (SDSL) technology and Electron Paramagnetic Resonance (EPR) spectroscopy. The acquired mobility, accessibility and orientation information in membrane will be integrated to derive a three dimensional structural model of the transmembrane domain of Rv3882c. Successful implementation of this project will not only yield valuable information for structural determination of Rv3882c, but also provide deeper insights of the protein secretion system and pathogenic mechanism of Mycobacterium tuberculosis. Also, this project will provide method of using EPR as the tool for structural studies of other membrane proteins.", "\u8d1f\u8d23\u4eba\u804c\u79f0": "\u526f\u7814\u7a76\u5458"}, {"h": "", "\u9879\u76ee\u540d\u79f0": "\u771f\u6838\u751f\u7269mRNA\u8f6c\u5f55\u51fa\u6838\u590d\u5408\u7269TREX-1\u7684\u7ed3\u6784\u4e0e\u529f\u80fd\u7814\u7a76", "\u6279\u51c6\u53f7": "31500612", "\u9879\u76ee\u7c7b\u522b": "\u9752\u5e74\u79d1\u5b66\u57fa\u91d1\u9879\u76ee", "\u4f9d\u6258\u5355\u4f4d": "\u8bb8\u660c\u5b66\u9662", "\u9879\u76ee\u8d1f\u8d23\u4eba": "\u82cf\u6d4b\u6d0b", "\u8d44\u52a9\u7ecf\u8d39(\u4e07\u5143)": "20", "\u6279\u51c6\u5e74\u5ea6": "2015", "\u5173\u952e\u8bcd": "mRNA\u8f6c\u5f55\u51fa\u6838\u590d\u5408\u7269\uff1bTHO\u590d\u5408\u7269\uff1b\u86cb\u767d\u8d28\u7ed3\u6784\u751f\u7269\u5b66\uff1bX-\u5c04\u7ebf\u6676\u4f53\u5b66\uff1b\u51b7\u51bb\u7535\u955c", "\u662f\u5426\u7ed3\u9898": "\u662f", "\u7814\u7a76\u6210\u679c(\u671f\u520a\u8bba\u6587;\u4f1a\u8bae\u8bba\u6587;\u8457\u4f5c;\u5956\u52b1;\u4e13\u5229)": "0;0;0;0;0", "\u4f9d\u6258\u5355\u4f4dID": "400411", "\u9879\u76ee\u8d1f\u8d23\u4ebaID": "100181698", "\u9879\u76ee\u7c7b\u522b\u4ee3\u7801": "630", "\u7533\u8bf7\u4ee3\u7801": "C050101", "\u8d77\u6b62\u5e74\u6708": "2016-01\u81f32018-12", "\u4e2d\u6587\u6458\u8981": "\u771f\u6838\u751f\u7269mRNA\u8f6c\u5f55\u51fa\u6838\u590d\u5408\u7269TREX-1\u5e7f\u6cdb\u5b58\u5728\u4e8e\u4ece\u9175\u6bcd\u5230\u54fa\u4e73\u52a8\u7269\u4e2d\uff0c\u53c2\u4e0emRNA\u7684\u8f6c\u5f55\u3001\u8f6c\u5f55\u540e\u52a0\u5de5\u548c\u51fa\u6838\u8fd0\u8f93\u7b49\u4e00\u7cfb\u5217\u8fc7\u7a0b\u3002\u6709\u62a5\u9053\u6307\u51fa\uff0cTREX-1\u590d\u5408\u7269\u7ec4\u5206\u5728\u5f88\u591a\u764c\u75c7\u7ec4\u7ec7\u4e2d\u68c0\u6d4b\u5230\u8868\u8fbe\u5f02\u5e38\u3002TREX-1\u590d\u5408\u7269\u5728\u771f\u6838\u751f\u7269\u4e2d\u4fdd\u5b88\u6027\u8f83\u9ad8\uff0c\u9175\u6bcd\u6e90TREX-1\u590d\u5408\u7269\u7531Sub2\u3001Yra1\u548cTHO\u590d\u5408\u7269\u7ec4\u6210\uff0c\u4eba\u6e90TREX-1\u590d\u5408\u7269\u7531Uap56\u3001Yra1\u4ee5\u53ca\u4eba\u6e90THO\u590d\u5408\u7269\u7ec4\u6210\u3002\u76ee\u524d\uff0c\u7f3a\u4e4fTREX-1\u590d\u5408\u7269\u7684\u9ad8\u5206\u8fa8\u7387\u4e09\u7ef4\u7ed3\u6784\uff0c\u8fd9\u6781\u5927\u7684\u963b\u788d\u4e86\u5bf9\u5176\u53c2\u4e0epre-mRNA\u52a0\u5de5\u5206\u5b50\u673a\u7406\u7684\u6df1\u5165\u7814\u7a76\u3002\u6211\u4eec\u4e4b\u524d\u7684\u7814\u7a76\u901a\u8fc7\u6606\u866b\u6746\u72b6\u75c5\u6bd2\u4f53\u5916\u91cd\u7ec4\u8868\u8fbe\u83b7\u5f97\u4e86\u9ad8\u7eaf\u5ea6\u7684\u9175\u6bcd\u6e90THO\u590d\u5408\u7269\u3002\u5728\u6b64\u57fa\u7840\u4e0a\uff0c\u672c\u9879\u76ee\u62df\u5bf9\u9175\u6bcd\u548c\u4eba\u6e90\u7684TREX-1\u590d\u5408\u7269\u8fdb\u884c\u7ec4\u88c5\u4e0e\u7eaf\u5316\uff0c\u901a\u8fc7\u7ed3\u5408\u86cb\u767d\u8d28X\u5c04\u7ebf\u6676\u4f53\u5b66\u548c\u51b7\u51bb\u7535\u955c\u6280\u672f\uff0c\u4ee5\u671f\u83b7\u5f97TREX-1\u590d\u5408\u7269\u9ad8\u5206\u8fa8\u7387\u4e09\u7ef4\u7ed3\u6784\uff0c\u5e76\u8f85\u4ee5\u751f\u7269\u5316\u5b66\u548c\u7ec6\u80de\u751f\u7269\u5b66\u6280\u672f\uff0c\u7814\u7a76\u5176\u7ec4\u88c5\u53ca\u53c2\u4e0emRNA\u51fa\u6838\u7684\u5206\u5b50\u673a\u5236\u3002", "\u82f1\u6587\u6458\u8981": "Eukaryotic mRNA TRanscription/EXport complex-1 (TREX-1 complex) is evolutionarily conserved multi-protein complex from yeast to human, participating in mRNA transcription, post-transcription processing and export. Previous report indicated that different protein component of TREX-1 complex has dysregulated expressed in different cancer specimens. Yeast TREX-1 complex consists Sub2, Yra1 and THO complex, while human TREX-1 complex consists Uap56 (yeast Sub2 homologous protein), Aly (yeast Yra1 homologous protein) and human THO complex. The detail mechanism of how TREX-1 complex participate pre-mRNA maturation and export is still obscurity, due to the miss of high-resolution 3D structural model of TREX-1 complex. In previous study, we get highly purified yeast THO complex through recombinant baculovirus expression system. Based on these, we try to reconstitute yeast and human TREX-1 complex in vivo and in vitro, through protein X-ray crystallography and cyro-EM technology, aim to get high-resolution 3D structure of TREX-1 complex. We also try to use biochemical and cell biology method to investigate the molecular mechanism of TREX-1 assembling and its participation mRNA export.", "\u8d1f\u8d23\u4eba\u804c\u79f0": "\u8bb2\u5e08"}, {"h": "", "\u9879\u76ee\u540d\u79f0": "\u4e00\u79cd\u65b0\u7684\u8461\u8404\u7cd6\u8131\u6c22\u9176FAD-GDH\u7684\u6676\u4f53\u7ed3\u6784\u4e0e\u50ac\u5316\u673a\u5236\u7814\u7a76", "\u6279\u51c6\u53f7": "31560244", "\u9879\u76ee\u7c7b\u522b": "\u5730\u533a\u79d1\u5b66\u57fa\u91d1\u9879\u76ee", "\u4f9d\u6258\u5355\u4f4d": "\u9075\u4e49\u533b\u79d1\u5927\u5b66", "\u9879\u76ee\u8d1f\u8d23\u4eba": "\u6768\u6108\u4e30", "\u8d44\u52a9\u7ecf\u8d39(\u4e07\u5143)": "40", "\u6279\u51c6\u5e74\u5ea6": "2015", "\u5173\u952e\u8bcd": "", "\u662f\u5426\u7ed3\u9898": "\u5426", "\u7814\u7a76\u6210\u679c(\u671f\u520a\u8bba\u6587;\u4f1a\u8bae\u8bba\u6587;\u8457\u4f5c;\u5956\u52b1;\u4e13\u5229)": "0;0;0;0;0", "\u4f9d\u6258\u5355\u4f4dID": "", "\u9879\u76ee\u8d1f\u8d23\u4ebaID": "", 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Ionic glutamate acceptor 2 (GluA2) is involved in many important physiological and pathological processes in the brain. GluA2 is tetrameric (dimer of dimer), and its ligand binding domain (LBD) dimer plays a key role in the ligand gating of GluA2. As the LBD only weakly dimerizes by itself, there has been few studies on the ensemble structure of LBD dimer. We found that the LBD dimer adopts an array of relative orientations as the GluA2 shifts into the desensitized state. We thus propose to determine the ensemble structure of LBD dimer. We will use the CXMS (chemical cross-linking of proteins coupled with mass spectrometry analysis) analysis to obtain a low-resolution picture. Conjointly, we will use PRE (paramagnetic relaxation enhancement) NMR to further characterize the ensemble structure of LBD dimer, and use SAXS (small-angle x-ray scattering) to assess the relative populations of each conformational state. Based on the structural characterization, we will mutate key interfacial residues that may perturb the ensemble structure of LBD dimer, which will be confirmed by electrophysiological analyses. Together, we will illustrate how the structural change of LBD dimer accompanies the desensitization of GluA2. 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There is no cure and no available treatments to stop this disease progression. Today, mutations in LRRK2 are the most prevalent known genetic causes of Parkinson\u2019s disease, for both familial and sporadic cases. In spite of the intensive efforts over the past decade, the molecular role of LRRK2 in disease pathogenesis, its function, and the effects of disease-causing mutations remain unknown. Understanding the underlying mechanism of LRRK2 normal function and how it is affected by the disease-associated mutations will reveal novel mechanism-based therapeutic strategies. In addition to LRRK2 being associated with PD and being the most promising drug target for the disease, LRRK2 is an immensely intriguing protein, in that it has two enzymatic activities (GTPase activity and Kinase activity) that, together with other non-enzymatic domains, potentially represent a unique example of an intramolecular signaling system. The concept of the Roc GTPase domain functioning as a molecular switch regulating the overall activity of LRRK2 is conceptually interesting from a biochemical perspective, and it is the key to LRRK2\u2019s normal function and disease process. In addition to the relatively wide prevalence of LRRK2 in PD, it is the most attractive target for drug discovery, because over-activation of its kinase activity is linked to disease pathogenesis, and it is an enzyme with active sites well suited for binding potential drugs. Indeed, LRRK2 kinase activity was effectively inhibited by broad kinase inhibitors that compete for ATP in the ATP-binding pocket. However, their translation into the clinic has been difficult due to adverse effects. Various potential alternative strategies are being considered, including targeting the Roc domain. This proposed study seeks to define the structures of ROC domain and its mutants to understand the GTP hydrolysis mechanism and mutations pathogenesis by using X-ray diffraction crystallography, protein biochemistry and biophysics approaches, which could provide insight into locations on LRRK2 structures that are suitable for mechanism-based drug discovery.", "\u8d1f\u8d23\u4eba\u804c\u79f0": "\u526f\u6559\u6388"}, {"\u9879\u76ee\u540d\u79f0": "\u7ebf\u6027\u6cdb\u7d20\u94fe\u7ec4\u88c5\u590d\u5408\u7269(LUBAC)\u7684\u8c03\u8282\u673a\u5236\u7814\u7a76", "\u6279\u51c6\u53f7": "31500597", "\u9879\u76ee\u7c7b\u522b": "\u9752\u5e74\u79d1\u5b66\u57fa\u91d1\u9879\u76ee", "\u4f9d\u6258\u5355\u4f4d": "\u4e2d\u56fd\u79d1\u5b66\u9662\u4e0a\u6d77\u6709\u673a\u5316\u5b66\u7814\u7a76\u6240", "\u9879\u76ee\u8d1f\u8d23\u4eba": "\u5218\u5efa\u5e73", "\u8d44\u52a9\u7ecf\u8d39(\u4e07\u5143)": "20", "\u6279\u51c6\u5e74\u5ea6": "2015", "\u5173\u952e\u8bcd": "\u86cb\u767d\u8d28\u590d\u5408\u7269\uff1bX\u5c04\u7ebf\u6676\u4f53\u884d\u5c04\uff1b\u6cdb\u7d20\u5316\uff1b\u80bf\u7624\u574f\u6b7b\u56e0\u5b50TNF\u03b1\uff1b\u7ec6\u80de\u6b7b\u4ea1", "\u662f\u5426\u7ed3\u9898": "\u662f", "\u7814\u7a76\u6210\u679c(\u671f\u520a\u8bba\u6587;\u4f1a\u8bae\u8bba\u6587;\u8457\u4f5c;\u5956\u52b1;\u4e13\u5229)": "4;0;0;0;0", "\u4f9d\u6258\u5355\u4f4dID": "400014", "\u9879\u76ee\u8d1f\u8d23\u4ebaID": "100193226", "\u9879\u76ee\u7c7b\u522b\u4ee3\u7801": "630", "\u7533\u8bf7\u4ee3\u7801": "C050101", "\u8d77\u6b62\u5e74\u6708": "2016-01\u81f32018-12", "\u4e2d\u6587\u6458\u8981": "\u7ebf\u6027\u6cdb\u7d20\u5316\u662f\u4e00\u7c7b\u5e7f\u6cdb\u53c2\u4e0e\u708e\u75c7\u548c\u5148\u5929\u514d\u75ab\u7684\u65b0\u578b\u6cdb\u7d20\u5316\u4fee\u9970\u3002\u8fc4\u4eca\u552f\u4e00\u7684\u7ebf\u6027\u6cdb\u7d20\u94feE3\u8fde\u63a5\u9176LUBAC\u590d\u5408\u7269\u7531\u8c03\u8282\u4e9a\u57faSharpin\u3001HOIL1\u548c\u50ac\u5316\u4e9a\u57faHOIP\u7ec4\u6210\u3002\u5355\u72ec\u7684HOIP\u5904\u4e8e\u81ea\u6291\u5236\u72b6\u6001\uff0c\u4f46\u53ef\u4ee5\u88abSharpin\u6216HOIL1\u6fc0\u6d3b\u3002\u7136\u800c\uff0cHOIP\u7684\u81ea\u6291\u5236\u548c\u6fc0\u6d3b\u3001\u4e0eSharpin\u7684\u76f8\u4e92\u4f5c\u7528\u673a\u5236\u4ecd\u7136\u672a\u77e5\u3002Sharpin\u7f3a\u5931\u5c0f\u9f20\u8868\u73b0\u51fa\u591a\u5668\u5b98\u708e\u75c7\u548cTNF\u03b1\u901a\u8def\u5f02\u5e38\u3002\u4e3a\u4e86\u9610\u660eLUBAC\u590d\u5408\u7269\u7684\u8c03\u63a7\u673a\u5236\uff0c\u672c\u7533\u8bf7\u8ba1\u5212\u89e3\u6790\u81ea\u6291\u5236\u548c\u6fc0\u6d3b\u72b6\u6001\u7684HOIP\u50ac\u5316\u6838\u5fc3\u7247\u6bb5\uff0c\u4ee5\u53caSharpin/HOIP\u590d\u5408\u7269\u7684\u7ed3\u6784\uff0c\u63ed\u793aHOIP\u7684\u81ea\u6291\u5236\u548c\u6fc0\u6d3b\u673a\u5236\uff0c\u5e76\u8bbe\u8ba1\u70b9\u7a81\u53d8\u89e3\u9664\u81ea\u6291\u5236\u6216\u8005\u7834\u574fSharpin\u5bf9HOIP\u7684\u6fc0\u6d3b\uff0c\u7814\u7a76\u76f8\u5e94\u7a81\u53d8\u4f53\u5bf9\u7ec6\u80de\u6b7b\u4ea1\u6216RIP1\u7ebf\u6027\u6cdb\u7d20\u5316\u7684\u5f71\u54cd\uff0c\u4ee5\u68c0\u9a8c\u6211\u4eec\u7684\u5047\u8bf4\uff1aSharpin/HOIP\u590d\u5408\u7269\u5bf9RIP1\u7684\u7ebf\u6027\u6cdb\u7d20\u5316\u51b3\u5b9a\u4e86TNF\u03b1\u901a\u8def\u7684\u6700\u7ec8\u6548\u5e94\u2014\u2014\u708e\u75c7\u6216\u7ec6\u80de\u6b7b\u4ea1\u3002\u73b0\u6709\u5de5\u4f5c\u8fdb\u5c55\u4e3a\u5b9e\u73b0\u4e0a\u8ff0\u76ee\u6807\u5960\u5b9a\u4e86\u575a\u5b9e\u7684\u57fa\u7840\u3002", "\u82f1\u6587\u6458\u8981": "Linear ubiquitination, a recently discovered novel type of ubiquitination, is extensively involved in numerous signaling pathways related to inflammation and innate immune. Linear ubiquitin chain assembly complex (LUBAC) is the sole identified E3 ubiquitin ligase that catalyzes the formation of linear poly-ubiquitin chain. It consists of two regulatory subunits Sharpin and HOIL1 as well as one catalytic subunit HOIP. The isolated HOIP is in an auto-inhibited state, but it can be activated by Sharpin or HOIL1 to sufficiently promote the linear ubiquitination of target substrates. However, the molecular mechanisms underlying the the auto-inhibition of HOIP, its activation by Sharpin or HOIL1, and the interaction between HOIP and Sharpin are largely unknown. Previous studies indicated that loss of Sharpin in the mouse caused immunodeficiency and multi-organ inflammation, and severely inhibited the linear ubiquitination of TNF\u03b1 receptor signaling complex. Based on these findings, we propose a hypothesis: the linear ubiquitination level of RIP1 catalyzed by Sharpin/HOIP complex determines the outcome of TNF\u03b1 signaling\u2014inflammation or cell death. To further understand the regulatory mechanism of LUBAC complex, we aimed to solve the structures of the catalytic fragment of HOIP either in auto-inhibited or in activated states as well as the Sharpin/HOIP complex, thereby to uncover the auto-inhibition and activation mechanism of HOIP. Based on the solved structures, we will design point mutations to specifically disrupt the auto-inhibition or the trans-activation of HOIP mediated by Sharpin; we will further test our hypothesis by assessing the impact of these mutations on the linear ubiquitination level of RIP1 and the TNF\u03b1 induced cell death. Our current research progress has laid the foundation for us to pursue the scientific goals in this proposal.", "\u8d1f\u8d23\u4eba\u804c\u79f0": "\u526f\u7814\u7a76\u5458"}, {"\u9879\u76ee\u540d\u79f0": "\u8f6c\u5f55\u56e0\u5b50CcmR\u8c03\u63a7\u84dd\u7ec6\u83cc\u78b3\u6d53\u7f29\u673a\u5236\u7684\u7ed3\u6784\u751f\u7269\u5b66\u57fa\u7840", "\u6279\u51c6\u53f7": "31500598", "\u9879\u76ee\u7c7b\u522b": "\u9752\u5e74\u79d1\u5b66\u57fa\u91d1\u9879\u76ee", "\u4f9d\u6258\u5355\u4f4d": "\u4e2d\u56fd\u79d1\u5b66\u6280\u672f\u5927\u5b66", "\u9879\u76ee\u8d1f\u8d23\u4eba": "\u6210\u671b", "\u8d44\u52a9\u7ecf\u8d39(\u4e07\u5143)": "20", "\u6279\u51c6\u5e74\u5ea6": "2015", "\u5173\u952e\u8bcd": "\u84dd\u85fb\uff1b\u78b3\u6d53\u7f29\u673a\u5236\uff1b\u8f6c\u5f55\u8c03\u63a7\uff1b\u6676\u4f53\u7ed3\u6784\uff1b\u5f02\u6784\u6548\u5e94", "\u662f\u5426\u7ed3\u9898": "\u662f", "\u7814\u7a76\u6210\u679c(\u671f\u520a\u8bba\u6587;\u4f1a\u8bae\u8bba\u6587;\u8457\u4f5c;\u5956\u52b1;\u4e13\u5229)": "1;0;0;0;0", "\u4f9d\u6258\u5355\u4f4dID": "200654", "\u9879\u76ee\u8d1f\u8d23\u4ebaID": "100047316", "\u9879\u76ee\u7c7b\u522b\u4ee3\u7801": "630", "\u7533\u8bf7\u4ee3\u7801": "C050101", "\u8d77\u6b62\u5e74\u6708": "2016-01\u81f32018-12", "\u4e2d\u6587\u6458\u8981": "\u84dd\u7ec6\u83cc\u662f\u88ab\u5e7f\u6cdb\u7528\u4e8e\u5149\u5408\u4f5c\u7528\u548c\u78b3\u6d53\u7f29\u673a\u5236(CO2-concentrating mechanism, CCM)\u7814\u7a76\u7684\u91cd\u8981\u6a21\u5f0f\u751f\u7269\u3002CcmR\u662f\u96c6\u80de\u85fbPCC6803\u4e2d\u7684\u4e00\u4e2a\u8c03\u63a7\u78b3\u6d53\u7f29\u673a\u5236\u7684\u5168\u5c40\u6027\u8f6c\u5f55\u56e0\u5b50\uff0c\u5728\u4f4e\u78b3\u4fe1\u53f7\u4e0b\u89e3\u9664\u5bf9CCM\u76f8\u5173\u57fa\u56e0\u7684\u6291\u5236\uff0c\u5f15\u8d77\u8868\u8fbe\u4e0a\u8c03\uff0c\u4fc3\u8fdbCO2\u7684\u5438\u6536\uff0c\u4fdd\u8bc1\u5149\u5408\u4f5c\u7528\u7684\u987a\u5229\u8fdb\u884c\u3002\u6211\u4eec\u5c06\u4ee5CcmR apo-form\u56db\u805a\u4f53\u6676\u4f53\u7ed3\u6784\u4e3a\u57fa\u7840\uff0c\u7efc\u5408\u5229\u7528\u751f\u7269\u4fe1\u606f\u5b66\u3001\u751f\u7269\u5316\u5b66\u3001\u5206\u5b50\u751f\u7269\u5b66\u4ee5\u53ca\u7ed3\u6784\u751f\u7269\u5b66\u624b\u6bb5\uff0c\u5bf9CcmR\u4e0eDNA\u548c/\u6216\u4fe1\u53f7\u5206\u5b50\u7684\u76f8\u4e92\u4f5c\u7528\u53ca\u5176\u4e8c\u5143\u548c\u4e09\u5143\u6676\u4f53\u7ed3\u6784\u8fdb\u884c\u7cfb\u7edf\u7814\u7a76\uff0c\u4ee5\u671f\u63ed\u793aCcmR\u7684\u522b\u6784\u673a\u7406\uff0c\u5e76\u57fa\u4e8eCcmR\u7279\u5f02\u6027\u8bc6\u522b\u7684DNA\u5e8f\u5217\u9274\u5b9a\u5176\u8c03\u63a7\u7684\u4e0b\u6e38\u57fa\u56e0\u7f51\u7edc\u3002\u8be5\u9879\u76ee\u5c06\u9610\u660eCcmR\u7684\u8c03\u63a7\u78b3\u6d53\u7f29\u673a\u5236\u7684\u7ed3\u6784\u57fa\u7840\uff0c\u6709\u671b\u4e3a\u751f\u6001\u5e73\u8861\u548c\u519c\u4e1a\u751f\u4ea7\u63d0\u4f9b\u7406\u8bba\u6307\u5bfc\u3002", "\u82f1\u6587\u6458\u8981": "Cyanobacterium is an ideal model for studying the photosynthesis and CO2-concentration mechanism (CCM). The transcriptional factor CcmR was first identified in the cyanobacterium Synechocystis sp. PCC6803. It serves as a global controller to increase the expression of CCM related genes, which are suppressed at a high Ci concentration, thus augmenting the uptake of CO2 for the efficacy photosynthesis. Based on our previously determined crystal structure of the apo-form CcmR tetramer, we will systematically investigate the interactions of CcmR with the putative allosteric molecule and its binding DNA, by combining the methodologies of bioinformatics, biochemistry, molecular biology and structural biology. The findings will enable us to elucidate the CcmR allosteric mechanism, and to identify the gene network under the control of CcmR. This project will provide insights into the CCM regulated by CcmR, and might be helpful for guiding the ecological balance control and agricultural production in the future.", "\u8d1f\u8d23\u4eba\u804c\u79f0": "\u535a\u58eb\u540e"}, {"\u9879\u76ee\u540d\u79f0": "\u4e09\u7ef4\u8d85\u5206\u8fa8\u6280\u672f\u7814\u7a76\u7ec6\u80de\u6838\u5b54\u590d\u5408\u7269\u7684\u9009\u62e9\u6027\u5c4f\u969c\u5206\u5e03", "\u6279\u51c6\u53f7": "31500599", "\u9879\u76ee\u7c7b\u522b": "\u9752\u5e74\u79d1\u5b66\u57fa\u91d1\u9879\u76ee", "\u4f9d\u6258\u5355\u4f4d": "\u590d\u65e6\u5927\u5b66", "\u9879\u76ee\u8d1f\u8d23\u4eba": "\u9a6c\u70af", "\u8d44\u52a9\u7ecf\u8d39(\u4e07\u5143)": "21", "\u6279\u51c6\u5e74\u5ea6": "2015", "\u5173\u952e\u8bcd": "\u7ec6\u80de\u6838\u5b54\u590d\u5408\u7269\uff1bFG\u5c4f\u969c\uff1b\u5355\u5206\u5b50\uff1b\u8d85\u5206\u8fa8\u663e\u5fae\u955c\uff1b\u6838\u5b54\u4f20\u8f93", "\u662f\u5426\u7ed3\u9898": "\u662f", "\u7814\u7a76\u6210\u679c(\u671f\u520a\u8bba\u6587;\u4f1a\u8bae\u8bba\u6587;\u8457\u4f5c;\u5956\u52b1;\u4e13\u5229)": "9;0;0;0;0", "\u4f9d\u6258\u5355\u4f4dID": "201361", "\u9879\u76ee\u8d1f\u8d23\u4ebaID": "100162892", "\u9879\u76ee\u7c7b\u522b\u4ee3\u7801": "630", "\u7533\u8bf7\u4ee3\u7801": "C050101", "\u8d77\u6b62\u5e74\u6708": "2016-01\u81f32018-12", "\u4e2d\u6587\u6458\u8981": "\u7ec6\u80de\u6838\u5b54\u590d\u5408\u7269\uff08NPC\uff09\u662f\u771f\u6838\u7ec6\u80de\u4e2d\u8fde\u63a5\u7ec6\u80de\u8d28\u548c\u7ec6\u80de\u6838\u4e4b\u95f4\u7684\u9009\u62e9\u6027\u53cc\u5411\u901a\u9053\u3002\u7531\u5bcc\u542b\u82ef\u4e19\u6c28\u9178-\u7518\u6c28\u9178\uff08FG\uff09\u6c28\u57fa\u9178\u7247\u6bb5\u7684\u81ea\u7136\u975e\u6298\u53e0\u86cb\u767d\u6784\u6210\u7684FG-\u5c4f\u969c,\u9009\u62e9\u6027\u5730\u8c03\u63a7\u57fa\u56e0\u76f8\u5173\u7269\u8d28,\u6309\u7167\u88ab\u52a8\u8fd0\u8f93\u6216\u8005\u4e3b\u52a8\u4ecb\u5165\u8fd0\u8f93\u7684\u65b9\u5f0f\u8fdb\u51fa\u7ec6\u80de\u6838\u3002\u7136\u800c\uff0c\u6838\u5b54\u5185FG\u5c4f\u969c\u95f4\u7684\u76f8\u4e92\u4f5c\u7528\u4ee5\u53ca\u5206\u5e03\u72b6\u51b5\u4ecd\u7136\u662f\u6781\u5177\u4e89\u8bae\u7684\u91cd\u8981\u79d1\u5b66\u95ee\u9898\u3002\u672c\u9879\u76ee\u5c06\u57fa\u4e8e\u7533\u8bf7\u4eba\u53d1\u660e\u7684\u5355\u70b9\u659c\u5165\u5c04\u6fc0\u53d1\u5feb\u901f\u8d85\u5206\u8fa8\u663e\u5fae\u955c\u6280\u672f\uff0c\u7814\u7a76\u6838\u5b54\u4f20\u8f93\u86cb\u767d\u6216FG-\u86cb\u767d\u7247\u6bb5\u4e0eFG\u5c4f\u969c\u53cd\u5e94\u7684\u4e09\u7ef4\u5206\u5e03\u56fe\u50cf\uff0c\u4ece\u800c\u83b7\u5f97FG-\u5c4f\u969c\u5728\u7ec6\u80de\u6838\u5b54\u5185\u5b8c\u6574\u7684\u5206\u5e03\u60c5\u51b5\u3002\u53e6\u5916,\u8fdb\u4e00\u6b65\u68c0\u6d4b\u6838\u5b54\u4f20\u8f93\u86cb\u767d\u5bf9FG\u5c4f\u969c\u7684\u5206\u5e03\u5f71\u54cd\uff0c\u8ba8\u8bba\u6838\u5b54\u4f20\u8f93\u7684\u81ea\u8c03\u63a7\u673a\u5236\u3002\u8fd8\u5c06\u4ece\u4e0d\u540c\u4f20\u8f93\u86cb\u767d\u6216FG-\u7247\u6bb5\u5728\u4f20\u8f93\u8fc7\u7a0b\u4e2d\u7684\u7ade\u4e89\u6548\u679c\uff0c\u8ba8\u8bbaFG\u5c4f\u969c\u5bf9\u5404\u7c7b\u57fa\u56e0\u76f8\u5173\u7269\u8d28\u4f20\u8f93\u7684\u4f18\u5148\u987a\u5e8f\u3002\u6700\u7ec8\uff0c\u5b8c\u6574\u7684\u4e09\u7ef4FG\u5c4f\u969c\u5c06\u5bf9\u6838\u5b54\u86cb\u767d\u7f3a\u5931\u76f8\u5173\u7684\u767d\u8840\u75c5\u3001\u963f\u5c14\u5179\u6d77\u9ed8\u75c7\u7684\u81f4\u75c5\u673a\u5236\uff0c\u4ee5\u53ca\u5404\u79cd\u7c7b\u75c5\u6bd2\u7684\u4fb5\u5165\u673a\u5236\u7b49\u6838\u5b54\u76f8\u5173\u75c5\u7406\u673a\u5236\u6216\u57fa\u56e0\u6cbb\u7597\u63d0\u4f9b\u4fe1\u606f\u3002", "\u82f1\u6587\u6458\u8981": "The nuclear pore complexes (NPCs) selectively mediate the bidirectional trafficking of macromolecules between the cytoplasm and the nucleus in eukaryotic cells. The selective barrier formed by natively unfolded phenylalanine-glycine (FG) nucleoporins (Nups) inside the NPC allows for passive and facilitated transport through the NPC. However, the interactions that form the FG-barrier and their spatial distribution in the NPC remain unresolved. Based on the single-point edge-excitation sub-diffusion (SPEED) microscopy techniques, the applicant's invention, three-dimensionally map the interaction distributions between the fluorescent transport receptors (TRs) or FG-fragment and FG barrier. Then, we obtain fully information of the FG-barrier distribution in the NPC. The conformation change of the FG-barrier by TRs would be discussed as self-regulating mechanism of nucleocytoplasmic transport. Also from the competitive effects during different FG-fragments and transport proteins during the transport discuss priorities for the various gene related transport. Finally\uff0cthe complete three-dimensional FG-barrier distribution will provide information with leukemia, Alzheimer's disease pathogenesis, as well as various types of viruses invade mechanisms for NPC related pathological mechanism or gene therapy.", "\u8d1f\u8d23\u4eba\u804c\u79f0": "\u7814\u7a76\u5458"}, {"\u9879\u76ee\u540d\u79f0": "\u6210\u808c\u7ec6\u80de\u878d\u5408\u86cb\u767dmyomaker\u7684\u7ed3\u6784\u57fa\u7840\u4e0e\u4f5c\u7528\u673a\u7406", "\u6279\u51c6\u53f7": "31500600", "\u9879\u76ee\u7c7b\u522b": "\u9752\u5e74\u79d1\u5b66\u57fa\u91d1\u9879\u76ee", "\u4f9d\u6258\u5355\u4f4d": "\u6e05\u534e\u5927\u5b66", "\u9879\u76ee\u8d1f\u8d23\u4eba": "\u9f9a\u5fb7\u987a", "\u8d44\u52a9\u7ecf\u8d39(\u4e07\u5143)": "9", "\u6279\u51c6\u5e74\u5ea6": "2015", "\u5173\u952e\u8bcd": "\u819c\u86cb\u767d\uff1b\u5747\u4e00\u6027\uff1b\u6676\u4f53\u7b5b\u9009\uff1b\u7ed3\u6784\u89e3\u6790\uff1b\u6676\u4f53\u7ed3\u6784", "\u662f\u5426\u7ed3\u9898": "\u662f", "\u7814\u7a76\u6210\u679c(\u671f\u520a\u8bba\u6587;\u4f1a\u8bae\u8bba\u6587;\u8457\u4f5c;\u5956\u52b1;\u4e13\u5229)": "0;0;0;0;0", "\u4f9d\u6258\u5355\u4f4dID": "201260", "\u9879\u76ee\u8d1f\u8d23\u4ebaID": "100177698", "\u9879\u76ee\u7c7b\u522b\u4ee3\u7801": "630", "\u7533\u8bf7\u4ee3\u7801": "C050101", "\u8d77\u6b62\u5e74\u6708": "2016-01\u81f32016-12", "\u4e2d\u6587\u6458\u8981": "Myomaker\u662f\u65b0\u53d1\u73b0\u7684\u4e00\u79cd\u53ef\u4ee5\u76f4\u63a5\u8c03\u63a7\u6210\u808c\u7ec6\u80de\u878d\u5408\u548c\u808c\u8089\u518d\u751f\u7684\u86cb\u767d\uff0c\u8fd9\u662f\u54fa\u4e73\u52a8\u7269\u7ec6\u80de\u4e2d\u552f\u4e00\u4e00\u4e2a\u88ab\u9274\u5b9a\u7684\u808c\u8089\u7279\u5f02\u6027\u7684\u8c03\u8282\u86cb\u767d\u3002\u5b83\u4fc3\u8fdb\u6210\u808c\u7ec6\u80de\u878d\u5408\u4ee5\u53ca\u808c\u8089\u518d\u751f\u7684\u6d3b\u6027\u4e3a\u53d7\u4f24\u540e\u7684\u808c\u8089\u518d\u751f\u63d0\u4f9b\u4e86\u65b0\u7684\u673a\u4f1a\uff0c\u4e3a\u808c\u8089\u6027\u75be\u75c5\u7684\u6cbb\u7597\u63d0\u4f9b\u4e86\u65b0\u7684\u601d\u8def\u3002\u7136\u800c\uff0c\u76ee\u524d\u5bf9\u5176\u53d1\u6325\u529f\u80fd\u7684\u5206\u5b50\u673a\u7406\u4ecd\u7136\u4e00\u65e0\u6240\u77e5\u3002\u672c\u9879\u76ee\u62df\u4ece\u7ed3\u6784\u751f\u7269\u5b66\u7684\u89d2\u5ea6\u51fa\u53d1\uff0c\u89e3\u6790\u5176\u6676\u4f53\u7ed3\u6784\uff0c\u63ed\u793a\u5176\u5206\u5b50\u4f5c\u7528\u673a\u7406\u3002", "\u82f1\u6587\u6458\u8981": "Myomaker, a new discovered myoblast fusion activator, which is the only identified muscle-specific protein that directly regulates myoblast fusion and muscle regeneration in mammals. These activities of myomaker provide new opportunities for muscle regeneration and new strategies for therapy of muscle diseases. However, the molecular mechanism of myomaker is still in the dark. The aim of this project is to determinate the crystal structure of myomaker and provide new insights into the functional mechanism of myomaker.", "\u8d1f\u8d23\u4eba\u804c\u79f0": "\u535a\u58eb\u540e"}, {"\u9879\u76ee\u540d\u79f0": "\u5e03\u6c0f\u9525\u866b\u4e2d\u53c2\u4e0e\u57fa\u56e0\u8f6c\u5f55\u8c03\u63a7\u7684PAF1\u590d\u5408\u7269\u7684\u7ed3\u6784\u548c\u529f\u80fd\u7814\u7a76", "\u6279\u51c6\u53f7": "31500601", "\u9879\u76ee\u7c7b\u522b": "\u9752\u5e74\u79d1\u5b66\u57fa\u91d1\u9879\u76ee", "\u4f9d\u6258\u5355\u4f4d": "\u4e2d\u56fd\u79d1\u5b66\u6280\u672f\u5927\u5b66", "\u9879\u76ee\u8d1f\u8d23\u4eba": "\u5ed6\u5584\u6656", "\u8d44\u52a9\u7ecf\u8d39(\u4e07\u5143)": "20", "\u6279\u51c6\u5e74\u5ea6": "2015", "\u5173\u952e\u8bcd": "PAF1\u590d\u5408\u7269\uff1b\u8f6c\u5f55\u8c03\u63a7\uff1b\u5e03\u6c0f\u9525\u866b\uff1b\u86cb\u767d\u8d28\u7ed3\u6784\uff1b\u86cb\u767d\u8d28\u76f8\u4e92\u4f5c\u7528", "\u662f\u5426\u7ed3\u9898": "\u662f", "\u7814\u7a76\u6210\u679c(\u671f\u520a\u8bba\u6587;\u4f1a\u8bae\u8bba\u6587;\u8457\u4f5c;\u5956\u52b1;\u4e13\u5229)": "11;0;0;0;1", "\u4f9d\u6258\u5355\u4f4dID": "200654", "\u9879\u76ee\u8d1f\u8d23\u4ebaID": "100186764", "\u9879\u76ee\u7c7b\u522b\u4ee3\u7801": "630", "\u7533\u8bf7\u4ee3\u7801": "C050101", "\u8d77\u6b62\u5e74\u6708": "2016-01\u81f32018-12", "\u4e2d\u6587\u6458\u8981": "\u771f\u6838\u751f\u7269\u57fa\u56e0\u8f6c\u5f55\u7684\u8c03\u63a7\u5728\u65f6\u95f4\u548c\u7a7a\u95f4\u4e0a\u90fd\u5177\u6709\u5f88\u9ad8\u7684\u590d\u6742\u5ea6\uff0c\u7ec6\u80de\u5185\u57fa\u56e0\u8f6c\u5f55\u8c03\u8282\u7684\u5f02\u5e38\u4e0e\u5404\u7c7b\u75be\u75c5\u5bc6\u5207\u76f8\u5173\u3002\u5728\u7814\u7a76\u8f6c\u5f55\u8c03\u8282\u7684\u8fc7\u7a0b\u4e2d\uff0c\u5927\u91cfRNA\u805a\u5408\u9176\u76f8\u5173\u86cb\u767d\u590d\u5408\u4f53\u88ab\u62a5\u9053\uff0c\u5176\u4e2dPAF1\u590d\u5408\u7269\uff08RNA polymerase II associated factor complex, PAF1C\uff09\u5c31\u662f\u6700\u8fd1\u53d1\u73b0\u7684\u4e00\u79cd\u3002PAF1\u590d\u5408\u7269\u542b\u6709\u81f3\u5c11 5\u4e2a\u4e0d\u540c\u7684\u86cb\u767d\u4e9a\u57fa\uff0c\u80fd\u591f\u534f\u540c\u5176\u4ed6\u7684\u8f6c\u5f55\u56e0\u5b50\u53ca\u7ec4\u86cb\u767d\u4fee\u9970\u9176\u6765\u8c03\u63a7\u8f6c\u5f55\u8fc7\u7a0b\u3002\u9525\u866b\u662f\u4e00\u7c7b\u5355\u7ec6\u80de\u771f\u6838\u539f\u751f\u751f\u7269\uff0c\u80fd\u591f\u5f15\u8d77\u591a\u79cd\u9525\u866b\u75c5\u3002\u76ee\u524d\u5728\u5e03\u6c0f\u9525\u866b\u5c5e\u4e2d\u53d1\u73b0\u7684PAF1\u590d\u5408\u4f53\u7ec4\u6210\u4e0e\u9ad8\u7b49\u771f\u6838\u751f\u7269\u4e0d\u5b8c\u5168\u4fdd\u5b88\uff0c\u53ef\u80fd\u6697\u793a\u4e86\u5e03\u6c0f\u9525\u866b\u7279\u6709\u7684\u57fa\u56e0\u8f6c\u5f55\u8c03\u8282\u65b9\u5f0f\u3002\u672c\u9879\u7814\u7a76\u5c06\u7ed3\u5408\u7ed3\u6784\u751f\u7269\u5b66\u548c\u7ec6\u80de\u751f\u7269\u5b66\u65b9\u6cd5\uff0c\u7814\u7a76\u5e03\u6c0f\u9525\u866b\u4e2dPAF1\u590d\u5408\u7269\u7684\u7ed3\u6784\u53ca\u5176\u5728\u57fa\u56e0\u8f6c\u5f55\u8c03\u63a7\u4e2d\u7684\u4f5c\u7528\u3002\u672c\u7814\u7a76\u4e0d\u4ec5\u5c06\u4e30\u5bcc\u6211\u4eec\u5bf9\u5e03\u6c0f\u9525\u866bPAF1\u590d\u5408\u7269\u548c\u57fa\u56e0\u8f6c\u5f55\u8c03\u63a7\u7684\u8ba4\u8bc6\uff0c\u5bf9\u4e8e\u6211\u4eec\u4e86\u89e3\u771f\u6838\u751f\u7269PAF1\u590d\u5408\u7269\u548c\u57fa\u56e0\u8f6c\u5f55\u8c03\u63a7\u7684\u8fdb\u5316\u4e5f\u5177\u6709\u91cd\u8981\u610f\u4e49\u3002", "\u82f1\u6587\u6458\u8981": "Eukaryotic gene transcription regulation is extremely complex in space and time. Any defect of transcription process is closely related to a variety of diseases. Many protein complexes have been reported during the study of transcription regulation, PAF1C (RNA polymerase II associated factor 1 complex) is such a complex discovered recently. PAF1C, contains at least 5 subunits. It participates in gene transcription regulation cooperatively with other transcription factors and histone modification enzymes. Trypanosomatids, the causative pathogens of trypanosomiasis, are a group of unicellular protozoa. The compositions of PAF1C of Trypanosoma brucei (T. brucei) is not fully conserved with that from higher eukaryotes, which may imply species-specific regulation pathway of gene transcription. Here, we are trying to explore the structure of PAF1C and its role in gene transcription regulation in T. brucei, by combining the techniques of structural biology and cell biology. This study will not only enrich our knowledge of PAF1C\u2019s role in transcription regulation in T. brucei, but also has important implications for our understanding of the evolution of eukaryotic PAF1 complex and gene transcription regulation.", "\u8d1f\u8d23\u4eba\u804c\u79f0": "\u526f\u7814\u7a76\u5458"}, {"\u9879\u76ee\u540d\u79f0": "\u94dc\u7eff\u5fae\u56ca\u85fb\u6c14\u56ca\u86cb\u767d\u7684\u7ed3\u6784\u548c\u529f\u80fd\u7814\u7a76", "\u6279\u51c6\u53f7": "31500602", "\u9879\u76ee\u7c7b\u522b": "\u9752\u5e74\u79d1\u5b66\u57fa\u91d1\u9879\u76ee", "\u4f9d\u6258\u5355\u4f4d": "\u4e2d\u56fd\u79d1\u5b66\u6280\u672f\u5927\u5b66", "\u9879\u76ee\u8d1f\u8d23\u4eba": "\u4ee3\u4e9a\u7537", "\u8d44\u52a9\u7ecf\u8d39(\u4e07\u5143)": "20", "\u6279\u51c6\u5e74\u5ea6": "2015", "\u5173\u952e\u8bcd": "\u94dc\u7eff\u5fae\u56ca\u85fb\uff1b\u6c14\u56ca\uff1b\u6c14\u56ca\u86cb\u767d\uff1b\u6676\u4f53\u7ed3\u6784\uff1b\u7ed3\u6784\u86cb\u767d", "\u662f\u5426\u7ed3\u9898": "\u662f", "\u7814\u7a76\u6210\u679c(\u671f\u520a\u8bba\u6587;\u4f1a\u8bae\u8bba\u6587;\u8457\u4f5c;\u5956\u52b1;\u4e13\u5229)": "0;0;0;0;0", "\u4f9d\u6258\u5355\u4f4dID": "200654", "\u9879\u76ee\u8d1f\u8d23\u4ebaID": "100047317", "\u9879\u76ee\u7c7b\u522b\u4ee3\u7801": "630", "\u7533\u8bf7\u4ee3\u7801": "C050101", "\u8d77\u6b62\u5e74\u6708": "2016-01\u81f32018-12", "\u4e2d\u6587\u6458\u8981": "\u94dc\u7eff\u5fae\u56ca\u85fb\u662f\u4e00\u79cd\u5355\u7ec6\u80de\u6d6e\u6e38\u84dd\u85fb\uff0c\u80fd\u5927\u91cf\u4ea7\u751f\u6c14\u56ca\uff0c\u8425\u517b\u4e30\u5bcc\u65f6\u5728\u6de1\u6c34\u6c34\u4f53\u8868\u9762\u805a\u96c6\u66b4\u53d1\u6c34\u534e\u3002\u6c14\u56ca\u662f\u4e00\u79cd\u5b8c\u5168\u7531\u86cb\u767d\u8d28\u7ec4\u6210\u7684\u4e2d\u7a7a\u3001\u5145\u6ee1\u6c14\u4f53\u7684\u60f0\u6027\u7ed3\u6784\u3002\u6c14\u56ca\u4e3a\u85fb\u7ec6\u80de\u63d0\u4f9b\u6d6e\u529b\uff0c\u4f7f\u5176\u81ea\u884c\u8c03\u8282\u5728\u81ea\u7136\u6c34\u4f53\u4e2d\u7684\u5782\u76f4\u4f4d\u7f6e\uff0c\u6f02\u6d6e\u5230\u6c27\u6c14\u548c\u5149\u7167\u90fd\u9002\u5b9c\u7684\u4f4d\u7f6e\u4ee5\u5229\u4e8e\u81ea\u8eab\u751f\u957f\u548c\u751f\u5883\u6b96\u6c11\u5316\u3002\u6c14\u56ca\u4e0d\u4ec5\u662f\u94dc\u7eff\u5fae\u56ca\u85fb\u80fd\u6210\u4e3a\u4f18\u52bf\u85fb\u79cd\u7684\u91cd\u8981\u539f\u56e0\u4e4b\u4e00\uff0c\u4e5f\u5728\u6c34\u534e\u7684\u66b4\u53d1\u8fc7\u7a0b\u4e2d\u8d77\u5230\u4e86\u8c03\u8282\u4f5c\u7528\u3002\u7136\u800c\uff0c\u4eba\u4eec\u81f3\u4eca\u5c1a\u672a\u5f04\u6e05\u6c14\u56ca\u7684\u7ed3\u6784\u53ca\u5176\u5408\u6210\u964d\u89e3\u673a\u5236\u3002\u4e3a\u4e86\u63a2\u7a76\u6c14\u56ca\u5408\u6210\u76f8\u5173\u86cb\u767d\u7684\u4e09\u7ef4\u7ed3\u6784\uff0c\u8fdb\u4e00\u6b65\u91cd\u6784\u6c14\u56ca\u8fd9\u4e00\u4e2d\u7a7a\u7ed3\u6784\u7684\u4e09\u7ef4\u9762\u8c8c\uff0c\u6211\u4eec\u4ee5\u94dc\u7eff\u5fae\u56ca\u85fbMicrocystis aeruginosa PCC 7806\u4e2d\u7684\u6c14\u56ca\u5408\u6210\u76f8\u5173\u7684\u4e00\u7ec4Gvp\u86cb\u767d\u4e3a\u7814\u7a76\u5bf9\u8c61\uff0c\u5229\u7528X\u5c04\u7ebf\u6676\u4f53\u5b66\u624b\u6bb5\u89e3\u6790\u5404\u4e2a\u6c14\u56ca\u86cb\u767d\u7684\u7ed3\u6784\uff0c\u5e76\u8054\u5408\u8fd0\u7528\u9ad8\u5206\u8fa8\u7387\u51b7\u51bb\u7535\u955c\uff0c\u86cb\u767d\u8d28\u514d\u75ab\u5370\u8ff9\u6cd5\u548c\u80f6\u4f53\u91d1\u6807\u8bb0\u7b49\u65b9\u6cd5\u6765\u5206\u6790\u5404\u7ed3\u6784\u86cb\u767d\u7684\u5177\u4f53\u5b9a\u4f4d\u3002\u8be5\u9879\u76ee\u5c06\u89e3\u6790\u6c14\u56ca\u539f\u5b50\u5206\u8fa8\u7387\u6c34\u5e73\u4e0a\u7684\u4e09\u7ef4\u7ed3\u6784\uff0c\u5bf9\u6cbb\u7406\u6c34\u534e\u66b4\u53d1\u6709\u4e00\u5b9a\u7406\u8bba\u6307\u5bfc\u610f\u4e49\u3002", "\u82f1\u6587\u6458\u8981": "Microcystis aeruginosa was investigated and identified as a planktonic unicellular cyanobacterium which is responsible for algal bloom in the freshwater environments. In Microcystis cells, an abundant production of intracellular structures, the gas vesicle, an inert, hollow and gas-filled structure, formed solely from proteins, provides cells with buoyancy and regulates their vertical distribution in natural waters. Cyanobacteria could float taxis toward air-liquid interfaces of water environments, positioning themselves at a depth with optimal light and oxygen supply for better growth, subsequent niche colonization and water-bloom formation. However, the fine structure of gas vesicle and its  biosynthesis/degradation mechanisms are still unclear. To determine three dimensional structures of gas vesicle proteins and remodeling the integral hollow structure, we are committed to solve structures of Gvp proteins from Microcystis aeruginosa PCC 7806 using X-ray crystallography. Moreover, in combination with high-resolution cryo-electron microscopy, we will investigate the localization of individual Gvp proteins by immunoblotting and immunogold labeling-based tomography. These findings will provide insights into structural characteristics of gas vesicle and the rational control of algal bloom.", "\u8d1f\u8d23\u4eba\u804c\u79f0": "\u535a\u58eb\u540e"}, {"\u9879\u76ee\u540d\u79f0": "\u819c\u73af\u5883\u5bf9\u819c\u86cb\u767dDAGK\u7ed3\u6784\u4e0e\u529f\u80fd\u7684\u5f71\u54cd", "\u6279\u51c6\u53f7": "31500603", "\u9879\u76ee\u7c7b\u522b": "\u9752\u5e74\u79d1\u5b66\u57fa\u91d1\u9879\u76ee", "\u4f9d\u6258\u5355\u4f4d": "\u4e2d\u56fd\u79d1\u5b66\u9662\u6b66\u6c49\u7269\u7406\u4e0e\u6570\u5b66\u7814\u7a76\u6240", "\u9879\u76ee\u8d1f\u8d23\u4eba": "\u9648\u8273\u53ef", "\u8d44\u52a9\u7ecf\u8d39(\u4e07\u5143)": "20", "\u6279\u51c6\u5e74\u5ea6": "2015", "\u5173\u952e\u8bcd": "\u819c\u86cb\u767d\u7ed3\u6784\uff1b\u56fa\u4f53\u6838\u78c1\u5171\u632f\uff1b\u5929\u7136\u819c\uff1b\u53bb\u57a2\u5242\uff1b\u7518\u6cb9\u4e8c\u8102\u6fc0\u9176", "\u662f\u5426\u7ed3\u9898": "\u662f", "\u7814\u7a76\u6210\u679c(\u671f\u520a\u8bba\u6587;\u4f1a\u8bae\u8bba\u6587;\u8457\u4f5c;\u5956\u52b1;\u4e13\u5229)": "3;0;0;0;0", "\u4f9d\u6258\u5355\u4f4dID": "201322", "\u9879\u76ee\u8d1f\u8d23\u4ebaID": "100150871", "\u9879\u76ee\u7c7b\u522b\u4ee3\u7801": "630", "\u7533\u8bf7\u4ee3\u7801": "C050101", "\u8d77\u6b62\u5e74\u6708": "2016-01\u81f32018-12", "\u4e2d\u6587\u6458\u8981": "\u819c\u86cb\u767d\u7684\u7ed3\u6784\u4e0e\u529f\u80fd\u6df1\u53d7\u6240\u5904\u73af\u5883\u7684\u5f71\u54cd\u3002\u76ee\u524d\uff0c\u5728PDB\u6570\u636e\u5e93\u4e2d\u6536\u5f55\u7684\u819c\u86cb\u767d\u7ed3\u678490%\u4ee5\u4e0a\u662f\u5728\u819c\u6a21\u62df\u73af\u5883\u2014\u53bb\u57a2\u5242\u80f6\u675f\u4e2d\u89e3\u6790\u7684\u3002\u7136\u800c\uff0c\u5728\u53bb\u57a2\u5242\u7684\u73af\u5883\u4e2d\uff0c\u819c\u86cb\u767d\u7684\u771f\u5b9e\u7ed3\u6784\u80fd\u5426\u88ab\u7ef4\u6301\u662f\u5907\u53d7\u7ed3\u6784\u751f\u7269\u5b66\u5bb6\u5173\u6ce8\u7684\u95ee\u9898\u3002\u5927\u80a0\u6746\u83cc\u7518\u6cb9\u4e8c\u8102\u6fc0\u9176(DAGK)\u662f\u4e00\u4e2a\u5f88\u91cd\u8981\u7684\u4e09\u8de8\u819c\u86cb\u767d\uff0c\u5176\u4e09\u7ef4\u7ed3\u6784\u5df2\u7ecf\u88ab\u6db2\u4f53\u6838\u78c1\u5171\u632f\u548cX-Ray\u6676\u4f53\u884d\u5c04\u7684\u65b9\u6cd5\u5728\u53bb\u57a2\u5242\u80f6\u675f\u6216\u8102\u8d28\u7acb\u65b9\u76f8\u4e2d\u6240\u89e3\u6790\uff0c\u7136\u800c\u7531\u4e8e\u73af\u5883\u7684\u4e0d\u540c\uff0c\u5f97\u5230\u7684\u7ed3\u6784\u5dee\u522b\u5f88\u5927\uff0c\u5e76\u4e14\u8fd9\u4e24\u79cd\u7ed3\u6784\u90fd\u4e0d\u662f\u5728DAGK\u7684\u5929\u7136\u819c\u73af\u5883\u4e2d\u8fdb\u884c\u89e3\u6790\u7684\u3002\u56fa\u4f53\u6838\u78c1\u5171\u632f\u6280\u672f\u53ef\u4ee5\u5728\u63a5\u8fd1\u819c\u86cb\u767d\u5929\u7136\u73af\u5883\u7684\u78f7\u8102\u53cc\u5c42\u819c\u4e2d\u89e3\u6790\u5176\u4e09\u7ef4\u7ed3\u6784\uff0c\u662f\u6d4b\u5b9a\u4e0e\u8bc1\u5b9e\u819c\u86cb\u767d\u7ed3\u6784\u7684\u6709\u529b\u5de5\u5177\u3002\u672c\u9879\u76ee\u62df\u91c7\u7528\u56fa\u4f53\u6838\u78c1\u5171\u632f\u6280\u672f\u5728\u5927\u80a0\u6746\u83cc\u78f7\u8102\u819c\u7684\u73af\u5883\u4e0b\u5bf9DAGK\u7684\u4e09\u7ef4\u7ed3\u6784\u8fdb\u884c\u89e3\u6790\uff0c\u5e76\u5206\u6790\u4e0d\u540c\u73af\u5883\u4e0bDAGK\u6d3b\u6027\u533a\u57df\u7684\u7ed3\u6784\u53d8\u5316\uff0c\u9610\u91ca\u819c\u86cb\u767d\u7ed3\u6784\u4e0e\u529f\u80fd\u5bf9\u819c\u73af\u5883\u7684\u4f9d\u8d56\u6027\u3002", "\u82f1\u6587\u6458\u8981": "The structures of membrane proteins are profoundly influenced by membrane\u2013protein interactions. To date, more than 90% structures of membrane protein in the PDB have been determined in membrane mimetic environments-detergent micelles. However, it is very difficult to obtain membrane mimetic environments that support the native structure and function of a membrane protein. Escherichia coli diacylglycerol kinase (DAGK) is a very important transmembrane protein of which three dimensional structure has been determined in detergent micelles or lipid cubic phase by solution-state NMR or X-Ray crystallography. Due to the different membrane mimetic environments, the two structures differ obviously. Solid-state NMR is a powerful tool for studying structures of membrane proteins in the native-like membrane environments. This project aims to use Solid-state NMR to determin the sturcture of DAGK in Escherichia coli total lipids bilayer. Then, we will expain the influence of membrane environments on membrane protein structure and function by comparation the structures of DAGK active domain in different membrane environments.", "\u8d1f\u8d23\u4eba\u804c\u79f0": "\u52a9\u7406\u7814\u7a76\u5458"}, {"\u9879\u76ee\u540d\u79f0": "\u4e0eALS/FTD\u76f8\u5173\u8054\u7684C9orf72\u516d\u6838\u82f7\u9178\u91cd\u590d\u6269\u589e\u5f62\u6210G-\u56db\u94fe\u4f53\u7684\u7ed3\u6784\u7814\u7a76", "\u6279\u51c6\u53f7": "31500604", "\u9879\u76ee\u7c7b\u522b": "\u9752\u5e74\u79d1\u5b66\u57fa\u91d1\u9879\u76ee", "\u4f9d\u6258\u5355\u4f4d": "\u9999\u6e2f\u79d1\u6280\u5927\u5b66\u6df1\u5733\u7814\u7a76\u9662", "\u9879\u76ee\u8d1f\u8d23\u4eba": "\u5468\u6ce2", "\u8d44\u52a9\u7ecf\u8d39(\u4e07\u5143)": "20", "\u6279\u51c6\u5e74\u5ea6": "2015", "\u5173\u952e\u8bcd": "\u6838\u78c1\u5171\u632f\uff1bG-\u56db\u94fe\u4f53\uff1bC9orf72\u516d\u6838\u82f7\u9178\u91cd\u590d\u6269\u589e\uff1b\u808c\u840e\u7f29\u6027\u4fa7\u7d22\u786c\u5316\u75c7\uff1b\u989d\u989e\u53f6\u75f4\u5446", "\u662f\u5426\u7ed3\u9898": "\u662f", "\u7814\u7a76\u6210\u679c(\u671f\u520a\u8bba\u6587;\u4f1a\u8bae\u8bba\u6587;\u8457\u4f5c;\u5956\u52b1;\u4e13\u5229)": "2;0;0;0;0", "\u4f9d\u6258\u5355\u4f4dID": "404024", "\u9879\u76ee\u8d1f\u8d23\u4ebaID": "100175543", "\u9879\u76ee\u7c7b\u522b\u4ee3\u7801": "630", "\u7533\u8bf7\u4ee3\u7801": "C050101", "\u8d77\u6b62\u5e74\u6708": "2016-01\u81f32018-12", "\u4e2d\u6587\u6458\u8981": "\u808c\u840e\u7f29\u6027\u4fa7\u7d22\u786c\u5316\u75c7\uff08ALS\uff09\u548c\u989d\u989e\u53f6\u75f4\u5446\uff08FTD\uff09\u662f\u4e25\u91cd\u7684\u795e\u7ecf\u9000\u884c\u6027\u75be\u75c5\u3002\u5728\u5bb6\u65cf\u6027\u6216\u6563\u53d1\u6027ALS/FTD\u60a3\u8005\u4e2d\uff0c\u4f4d\u4e8e9\u53f7\u67d3\u8272\u4f53\u7b2c72\u4e2a\u5f00\u653e\u9605\u8bfb\u6846\u57fa\u56e0\uff08C9orf72\uff09\u7684GGGGCC\u516d\u6838\u82f7\u9178\u91cd\u590d\u6269\u589e\uff08HRE\uff09\u662f\u6700\u5e38\u89c1\u7684\u9057\u4f20\u81f4\u75c5\u56e0\u5b50\u3002\u4ee5\u5f80\u7814\u7a76\u8868\u660e\uff0cC9orf72 HRE\u65e0\u8bba\u662f\u4f5c\u4e3aDNA\u6216\u8f6c\u5f55\u7684RNA\u4ea7\u7269\uff0c\u5747\u53ef\u6298\u53e0\u6210\u5177\u6709\u4e0d\u540c\u7ed3\u6784\u7684G-\u56db\u94fe\u4f53\uff0c\u5e76\u4e0eALS/FTD\u7684\u81f4\u75c5\u673a\u7406\u5bc6\u5207\u76f8\u5173\u3002\u7531\u4e8e\u7f3a\u4e4f\u76f8\u5173G-\u56db\u94fe\u4f53\u7684\u9ad8\u5206\u8fa8\u7387\u7ed3\u6784\u4fe1\u606f\uff0cC9orf72 HRE\u5f62\u6210G-\u56db\u94fe\u4f53\u7684\u5206\u5b50\u673a\u7406\u4ecd\u4e0d\u6e05\u695a\u3002\u672c\u7814\u7a76\u5c06\u5229\u7528\u6838\u78c1\u5171\u632f\u6280\u672f\u9996\u6b21\u83b7\u53d6C9orf72 HRE DNA\u53caRNA G-\u56db\u94fe\u4f53\u7684\u9ad8\u5206\u8fa8\u7387\u7ed3\u6784\uff0c\u5bf9\u4e8e\u5728ALS/FTD\u60a3\u8005\u4e2d\u7531\u4e8e\u6b64\u79cd\u7ed3\u6784\u5bfc\u81f4\u7684\u5f02\u5e38\u8f6c\u5f55\u4ea7\u7269\u8bf1\u53d1\u75be\u75c5\u7684\u5206\u5b50\u673a\u7406\u63d0\u4f9b\u6781\u6709\u4ef7\u503c\u7684\u4fe1\u606f\uff0c\u5e76\u4e14\u4e3a\u9488\u5bf9C9orf72 HRE G-\u56db\u94fe\u4f53\u8bbe\u8ba1\u5c0f\u5206\u5b50\u7528\u4ee5\u9776\u5411\u8c03\u8282ALS/ FTD\u7684\u53d1\u75c5\u673a\u5236\u5960\u5b9a\u5fc5\u8981\u7684\u7ed3\u6784\u5b66\u57fa\u7840\u3002", "\u82f1\u6587\u6458\u8981": "Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are devastating neurological diseases. Abnormal expansion of a hexanucleotide repeat, (GGGGCC)n, is the most common genetic cause of familial and sporadic forms of ALS and FTD. This nucleotide repeat element is located in a non-protein-coding region of the C9orf72 gene. Previous studies suggested that the C9orf72 hexanucleotide repeat expansion (HRE), either as DNA or the transcribed RNA, can fold into G-quadruplexes with distinct structures. It could also form transcriptionally induced RNA-DNA hybrids known as R-loops. These structural polymorphisms lead to C9orf72 HRE-containing abortive transcripts, which may aggregate and form RNA foci in patient cells. Despite the critical connection of C9orf72 HRE G-quadruplexes to the pathogenic mechanism of C9orf72 HRE-linked ALS/FTD, the molecular basis of G-quadruplex formation by C9orf72 HRE remains elusive..In this project, we plan to perform systematic biochemical and structural characterizations for C9orf72 HRE G-quadruplexes. First, we will determine the 3D structure of G-quadruplex formed by the C9orf72 HRE DNA. In our preliminary study, we successfully obtained a homogenous DNA sample, d(GGGGCC)4, which favored a monomeric G-quadruplex fold. We have determined the topology of this G-quadruplex DNA using the nuclear magnetic resonance (NMR) approach. It forms a chair-type G-quadruplex with a four-layer antiparallel G-tetra core and three edgewise loops, which is distinct from known structures of chair-type G-quadruplexes. We will further resolve its detailed structure using NMR techniques. We have also successfully obtained a homogeneous C9orf72 HRE RNA sample with sufficient quality for NMR structure determination. Unlike the monomeric d(GGGGCC)4 DNA, this RNA, r(GGGGCC)GGGG, is an asymmetric dimer. We will perform more NMR studies to obtain its 3D structure. As no structure of the C9orf72 HRE G-quadruplex has ever been solved, the structural information of C9orf72 HRE DNA/RNA G-quadruplexes to be obtained in the current project will provide valuable insights into the molecular mechanism of abortive transcripts formation by C9orf72 HRE and RNA foci appearance in ALS/FTD patients. The outcome of the proposed research will not only provide insight into the molecular mechanism underlying the C9orf72 HRE G-quadruplex formation in the etiology of ALS/FTD, but may also lay the necessary basis for designing small molecules that therapeutically target C9orf72 HRE G-quadruplexes for the modulation of ALS/FTD pathogenesis.", "\u8d1f\u8d23\u4eba\u804c\u79f0": "\u526f\u7814\u7a76\u5458"}, {"\u9879\u76ee\u540d\u79f0": "Sema-Plexin\u4fe1\u53f7\u901a\u8def\u4e2dFARP2\u7684\u7ed3\u6784\u4e0e\u529f\u80fd\u7814\u7a76", "\u6279\u51c6\u53f7": "31500605", "\u9879\u76ee\u7c7b\u522b": "\u9752\u5e74\u79d1\u5b66\u57fa\u91d1\u9879\u76ee", "\u4f9d\u6258\u5355\u4f4d": "\u534e\u4e2d\u79d1\u6280\u5927\u5b66", "\u9879\u76ee\u8d1f\u8d23\u4eba": "\u8d3a\u6653\u9759", "\u8d44\u52a9\u7ecf\u8d39(\u4e07\u5143)": "21", "\u6279\u51c6\u5e74\u5ea6": "2015", "\u5173\u952e\u8bcd": "\u86cb\u767d\u8d28\u7ed3\u6784\uff1b\u76f8\u4e92\u4f5c\u7528\uff1b\u8f74\u7a81\u5bfc\u5411", "\u662f\u5426\u7ed3\u9898": "\u662f", "\u7814\u7a76\u6210\u679c(\u671f\u520a\u8bba\u6587;\u4f1a\u8bae\u8bba\u6587;\u8457\u4f5c;\u5956\u52b1;\u4e13\u5229)": "2;0;0;0;0", "\u4f9d\u6258\u5355\u4f4dID": "100113", "\u9879\u76ee\u8d1f\u8d23\u4ebaID": "100154722", "\u9879\u76ee\u7c7b\u522b\u4ee3\u7801": "630", "\u7533\u8bf7\u4ee3\u7801": "C050101", "\u8d77\u6b62\u5e74\u6708": "2016-01\u81f32018-12", "\u4e2d\u6587\u6458\u8981": "\u795e\u7ecf\u7cfb\u7edf\u7684\u7cbe\u786e\u53d1\u80b2\u53d1\u5c55\u79bb\u4e0d\u5f00\u8f74\u7a81\u5bfc\u5411\u3002\u795e\u7ecf\u7ec6\u80de\u751f\u957f\u690e\u4e0a\u7684\u53d7\u4f53\u63a5\u53d7\u73af\u5883\u4e2d\u7684\u8f74\u7a81\u5bfc\u5411\u56e0\u5b50\u4f20\u9012\u7684\u4fe1\u53f7\uff0c\u7ecf\u8fc7\u4e00\u7cfb\u5217\u86cb\u767d\u7684\u4f20\u9012\uff0c\u6700\u540e\u4f5c\u7528\u4e8e\u7ec6\u80de\u9aa8\u67b6\u86cb\u767d\uff0c\u4ece\u800c\u5f71\u54cd\u751f\u957f\u690e\u7684\u8d70\u5411\u3002Semaphorin-Plexin \u901a\u8def\u662f\u5176\u4e2d\u91cd\u8981\u7684\u4fe1\u53f7\u901a\u8def\u4e4b\u4e00\uff0c\u6211\u4eec\u7684\u7814\u7a76\u91cd\u70b9\u662f\u8fd9\u4e00\u901a\u8def\u4e2dplexin\u7684\u4e0b\u6e38\u4e92\u4f5c\u86cb\u767dFARP2\u3002FARP2 N\u7aef\u7684FERM\u7ed3\u6784\u57df\u4ecb\u5bfc\u5b83\u4e0ePlexin\u4e4b\u95f4\u7684\u76f8\u4e92\u4f5c\u7528\uff0c\u4f46\u662f\u4e8c\u8005\u4e4b\u95f4\u7684\u4e92\u4f5c\u6a21\u5f0f\u4e0e\u5206\u5b50\u673a\u5236\u8fd8\u4e0d\u6e05\u695a\u3002\u672c\u9879\u76ee\u5c06\u5229\u7528\u6676\u4f53\u751f\u7269\u5b66\uff0c\u751f\u7269\u5316\u5b66\uff0c\u7ec6\u80de\u751f\u7269\u5b66\u7b49\u624b\u6bb5\uff0c\u5728\u7ed3\u6784\u4e0e\u529f\u80fd\u4e0a\u7814\u7a76FARP2\u53ca\u5176\u4e0ePlexin\u7684\u4e92\u4f5c\u5173\u7cfb\u548c\u5206\u5b50\u8c03\u63a7\u673a\u5236\uff0c\u4e3a\u8fdb\u4e00\u6b65\u7406\u89e3Sema-Plexin\u901a\u8def\u4e0b\u6e38\u4fe1\u53f7\u4f20\u5bfc\u673a\u5236\u63d0\u4f9b\u5206\u5b50\u4f9d\u636e\u3002\u6211\u4eec\u4e4b\u524d\u7684\u7ed3\u6784\u751f\u7269\u5b66\u7814\u7a76\u53d1\u73b0FARP2 \u7684DH-PH-PH\u7ed3\u6784\u57df\u662f\u4e00\u79cd\u4ee5\u81ea\u6211\u6291\u5236\u6784\u8c61\u5b58\u5728\u7684\u5c0fGTP\u9176\u7684\u9e1f\u6838\u82f7\u9178\u4ea4\u6362\u56e0\u5b50(GEF)\uff0c\u672c\u9879\u76ee\u5c06\u8fdb\u4e00\u6b65\u63a2\u8ba8\u5982\u4f55\u6fc0\u6d3bFARP2\u7684GEF\u6d3b\u6027\u3002", "\u82f1\u6587\u6458\u8981": "\u82f1\u6587\u6458\u8981.The correct wiring of the nervous system relies on the precise axon guidance. During development of the nervous system, axons are guided to their proper targets by sensing a variety of extracellular cues in the local environment. The receptor protein on the neuronal growth cones which is located at the tip of the growing axon, recognizes guidance cues. The signal finally selectively alters the stability of the actin cytoskeleton and microtubules that determine the rate and direction  of   axon  extension.  Semaphorin-Plexin  is  one  of  the  classic ligand/receptor systems involved in this process\uff0c and we will focus on FARP2, which is a downstream partner of Plexin A1. FARP2 interacts with Plexin A1 though its N terminal FERM domain, but how they bind is still not clear. We are using  the  combination  of  protein  X-ray  crystallography,  biochemical techniques and cell based assay to study the structure and function of FARP2 and its interaction and regulation with Plexin A1. Our research will help us to understand the molecular regulation mechanisms of downstream signal transduction of Sema-plexin pathway.  C terminal domain DH-PH-PH of FARP2 is an auto-inhibited Guanine nucleotide exchange factor (GEF) based on our previous studies, and we will study how to active GEF activity further.", "\u8d1f\u8d23\u4eba\u804c\u79f0": "\u6559\u6388"}, {"\u9879\u76ee\u540d\u79f0": "Tip49a/Tip49b\u53ca\u5176\u76f8\u5173\u590d\u5408\u7269\u7684\u51b7\u51bb\u7535\u955c\u7ed3\u6784\u7814\u7a76", "\u6279\u51c6\u53f7": "31500606", "\u9879\u76ee\u7c7b\u522b": "\u9752\u5e74\u79d1\u5b66\u57fa\u91d1\u9879\u76ee", "\u4f9d\u6258\u5355\u4f4d": "\u5fb7\u5dde\u5b66\u9662", "\u9879\u76ee\u8d1f\u8d23\u4eba": "\u5b8b\u5cf0", "\u8d44\u52a9\u7ecf\u8d39(\u4e07\u5143)": "20", "\u6279\u51c6\u5e74\u5ea6": "2015", "\u5173\u952e\u8bcd": "\u51b7\u51bb\u7535\u955c\uff1b\u5355\u9897\u7c92\u4e09\u7ef4\u91cd\u6784\uff1b\u86cb\u767d\u590d\u5408\u7269\u7ec4\u88c5", "\u662f\u5426\u7ed3\u9898": "\u662f", "\u7814\u7a76\u6210\u679c(\u671f\u520a\u8bba\u6587;\u4f1a\u8bae\u8bba\u6587;\u8457\u4f5c;\u5956\u52b1;\u4e13\u5229)": "4;0;0;0;0", "\u4f9d\u6258\u5355\u4f4dID": "400969", "\u9879\u76ee\u8d1f\u8d23\u4ebaID": "100181269", "\u9879\u76ee\u7c7b\u522b\u4ee3\u7801": "630", "\u7533\u8bf7\u4ee3\u7801": "C050101", "\u8d77\u6b62\u5e74\u6708": "2016-01\u81f32018-12", "\u4e2d\u6587\u6458\u8981": "Tip49a\u548cTip49b\u662fAAA+\u8d85\u5bb6\u65cf\u7684\u4e24\u4e2a\u86cb\u767d\uff0c\u5b83\u4eec\u4fdd\u5b88\u5730\u5b58\u5728\u4e8e\u4ece\u9175\u6bcd\u5230\u4eba\u7684\u591a\u4e2a\u7269\u79cd\u4e2d\uff0c\u5728\u7ec6\u80de\u5185\u901a\u5e38\u4ee5\u590d\u5408\u7269\u7684\u5f62\u5f0f\u5b58\u5728\u3002\u5b83\u4eec\u5728DNA\u635f\u4f24\u4fee\u590d\u3001\u8f6c\u5f55\u8c03\u63a7\u3001snoRNP\u6210\u719f\u3001\u67d3\u8272\u8d28\u91cd\u5851\u7b49\u751f\u547d\u6d3b\u52a8\u4e2d\u53d1\u6325\u91cd\u8981\u7684\u8c03\u63a7\u4f5c\u7528\uff0c\u4f46\u8fc4\u4eca\u4e3a\u6b62\u4ecd\u7136\u6ca1\u6709Tip49a/Tip49b\u5168\u957f\u86cb\u767d\u76f8\u5173\u590d\u5408\u7269\u7684\u7ed3\u6784\u62a5\u9053\u3002\u672c\u7814\u7a76\u62df\u4e3b\u8981\u5e94\u7528\u51b7\u51bb\u7535\u955c\u5355\u9897\u7c92\u4e09\u7ef4\u91cd\u6784\u6280\u672f\u89e3\u6790\u4eba\u6e90Tip49a/Tip49b\u53ca\u5176\u53c2\u4e0e\u5f62\u6210\u7684\u4e24\u79cd\u9ad8\u7ea7\u590d\u5408\u7269\uff08R2TP\u3001Tip49a/Tip49b-\u6838\u5c0f\u4f53\uff09\u7684\u9ad8\u7cbe\u5ea6\u4e09\u7ef4\u7ed3\u6784\uff0c\u5e76\u7ed3\u5408\u751f\u5316\u5b9e\u9a8c\u786e\u5b9aTip49a/Tip49b\u5728\u4e24\u79cd\u9ad8\u7ea7\u590d\u5408\u7269\u4e2d\u7684\u4f5c\u7528\u3002\u672c\u9879\u76ee\u7684\u7814\u7a76\u6210\u679c\u5c06\u4e3a\u7406\u89e3Tip49a/Tip49b\u5728snoRNP\u7ec4\u88c5\uff08R2TP\u590d\u5408\u7269\uff09\u548cATP\u4f9d\u8d56\u7684\u67d3\u8272\u8d28\u91cd\u5851\uff08Tip49a/Tip49b-\u6838\u5c0f\u4f53\u590d\u5408\u7269\uff09\u4e2d\u7684\u5de5\u4f5c\u673a\u5236\u63d0\u4f9b\u53ef\u9760\u7684\u7ed3\u6784\u4fe1\u606f\u3002", "\u82f1\u6587\u6458\u8981": "Tip49a and Tip49b are two structurally and functionally highly related proteins that belong to the AAA+ (ATPase Associated with diverse cellular Activities) superfamily. They are existed in many species of which ranging from yeast to human. Both Tip49a and Tip49b are conserved components of various multi-subunit complexes, which are linked to a wide range of cellular processes, such as DNA damage response, transcription regulation, snoRNP biogenesis and ATP-dependent chromatin remodeling. Despite their diverse roles, there is no available high resolution structure of full-length Tip49a/Tip49b protein complex. The mainly purpose of our research is to reveal the high resolution structures of dodecameric Tip49a/Tip49b and determine their functions in two larger complexes which containing them, R2TP and Tip49a/Tip49b-nucleosome complex, by using cryo-EM single particle analysis combining with biochemical and biophysical techniques. Our research will provide insights into the structural basis of Tip49a/Tip49b in mediating snoRNP biogenesis(R2TP complex) and ATP-dependent chromatin remodeling(Tip49a/Tip49b-nucleosome complex).", "\u8d1f\u8d23\u4eba\u804c\u79f0": "\u6559\u6388"}, {"\u9879\u76ee\u540d\u79f0": "\u7ed3\u6838\u5206\u679d\u6746\u83cc\u5206\u679d\u83cc\u9178\u5408\u6210\u9014\u5f84\u8131\u6c34\u9176HadABC\u590d\u5408\u7269\u4e0e\u591a\u79cd\u6297\u7ed3\u6838\u6291\u5236\u5242\u7684\u7ed3\u6784\u548c\u529f\u80fd\u7814\u7a76", "\u6279\u51c6\u53f7": "31500607", "\u9879\u76ee\u7c7b\u522b": "\u9752\u5e74\u79d1\u5b66\u57fa\u91d1\u9879\u76ee", "\u4f9d\u6258\u5355\u4f4d": "\u4e2d\u56fd\u79d1\u5b66\u9662\u4e0a\u6d77\u751f\u547d\u79d1\u5b66\u7814\u7a76\u9662", "\u9879\u76ee\u8d1f\u8d23\u4eba": "\u674e\u4fca", "\u8d44\u52a9\u7ecf\u8d39(\u4e07\u5143)": "20", "\u6279\u51c6\u5e74\u5ea6": "2015", "\u5173\u952e\u8bcd": "\u7ed3\u6838\u5206\u679d\u6746\u83cc\uff1b\u6676\u4f53\u7ed3\u6784\uff1b\u5206\u679d\u83cc\u9178\uff1b\u8131\u6c34\u9176\uff1b\u836f\u7269\u9776\u70b9", "\u662f\u5426\u7ed3\u9898": "\u662f", "\u7814\u7a76\u6210\u679c(\u671f\u520a\u8bba\u6587;\u4f1a\u8bae\u8bba\u6587;\u8457\u4f5c;\u5956\u52b1;\u4e13\u5229)": "3;0;0;0;0", "\u4f9d\u6258\u5355\u4f4dID": "201022", "\u9879\u76ee\u8d1f\u8d23\u4ebaID": "100175031", "\u9879\u76ee\u7c7b\u522b\u4ee3\u7801": "630", "\u7533\u8bf7\u4ee3\u7801": "C050101", "\u8d77\u6b62\u5e74\u6708": "2016-01\u81f32018-12", "\u4e2d\u6587\u6458\u8981": "\u7ed3\u6838\u75c5\u662f\u76ee\u524d\u4e16\u754c\u4e0a\u81f4\u6b7b\u7387\u6700\u9ad8\u3001\u4f20\u64ad\u8303\u56f4\u6700\u5e7f\u7684\u7ec6\u83cc\u6027\u75be\u75c5\u3002\u7ed3\u6838\u5206\u679d\u6746\u83cc\u662f\u5f15\u53d1\u7ed3\u6838\u75c5\u7684\u75c5\u539f\u83cc\uff0c\u7531\u4e8e\u8010\u591a\u836f\u83cc\u682a\uff08MDR-TB\uff09\u548c\u5e7f\u6cdb\u8010\u836f\u83cc\u682a\uff08XDR-TB\uff09\u7684\u51fa\u73b0\uff0c\u4f7f\u5f97\u73b0\u6709\u836f\u7269\u7684\u6cbb\u7597\u51e0\u4e4e\u5931\u6548\u3002\u56e0\u6b64\uff0c\u5bfb\u627e\u65b0\u7684\u836f\u7269\u9776\u70b9\u4ee5\u53ca\u7814\u7a76\u5168\u65b0\u4f5c\u7528\u673a\u5236\u7684\u5f3a\u529b\u6297\u7ed3\u6838\u836f\u7269\u5df2\u7ecf\u6210\u4e3a\u8feb\u5728\u7709\u776b\u7684\u91cd\u8981\u4efb\u52a1\u3002\u7531\u81f4\u5bc6\u7684\u5206\u679d\u83cc\u9178\u5c42\u6784\u6210\u7684\u7ec6\u80de\u58c1\u4f7f\u5f97\u7ed3\u6838\u5206\u679d\u6746\u83cc\u53ef\u4ee5\u9003\u907f\u514d\u75ab\u653b\u51fb\u548c\u6709\u5bb3\u7269\u8d28\u5165\u4fb5\u4ece\u800c\u80fd\u591f\u5b58\u6d3b\u3002\u8131\u6c22\u9176HadAB\u548cHadBC\u662fII\u578b\u5206\u679d\u83cc\u9178\u8102\u94fe\u5ef6\u4f38\u7cfb\u7edf\uff08FAS-II\uff09\u4e2d\u6700\u665a\u88ab\u53d1\u73b0\u7684\u4e24\u5bf9\u590d\u5408\u7269\uff0c\u4e5f\u662f\u4e00\u7ebf\u836f\u7269\u5f02\u70df\u80bc\u9776\u70b9InhA\u7684\u4e0b\u6e38\u86cb\u767d\u3002\u8fc4\u4eca\u4e3a\u6b62\uff0c\u5176\u4e09\u7ef4\u7ed3\u6784\u548c\u50ac\u5316\u673a\u5236\u5c1a\u4e0d\u6e05\u695a\u3002\u672c\u7814\u7a76\u9879\u76ee\u53ef\u4ee5\u586b\u8865\u8fd9\u65b9\u9762\u7684\u7a7a\u767d\uff0c\u4ece\u5206\u5b50\u6c34\u5e73\u4e0a\u63a8\u8fdb\u5176\u9176\u6d3b\u673a\u5236\u7684\u7814\u7a76\uff1b\u800cHadABC\u4e0e\u9ec4\u916e\u7c7b\u6291\u5236\u5242\u548c\u6297\u7ed3\u6838\u836f\u7269Isoxyl\u3001Thiacetazone\u590d\u5408\u7269\u7ed3\u6784\u7814\u7a76\u5c06\u63ed\u793a\u5176\u6297\u7ed3\u6838\u7684\u6291\u5236\u673a\u5236\uff0c\u5bf9\u57fa\u4e8eHadABC\u7684\u6297\u7ed3\u6838\u836f\u7269\u5f00\u53d1\u63d0\u4f9b\u91cd\u8981\u7ebf\u7d22\u548c\u53ef\u9760\u7684\u7ed3\u6784\u751f\u7269\u5b66\u57fa\u7840\u3002", "\u82f1\u6587\u6458\u8981": "Tuberculosis (TB) is the most lethal and widely spread bacterial infectious disease over the world, mainly caused by the pathogenic Mycobacterium tuberculosis (Mtb). Seriously, the emergence of Multi-drug resistant TB (MDR-TB) and extensively drug resistant TB (XDR-TB) make currently used drugs ineffective to cure TB. Therefore, developing novel and effective anti-TB drugs following research of newly found drug targets has already been an urgent and important mission now. Mtb is hard to kill under host immune attack and survives from toxicant invasion because of the dense and hydrophobic mycolic acid layer of cell wall. Both of HadAB and HadBC were the dehydratases, which were the last and latest identified piece of the type II fatty acid synthesis (FAS-II) system, involved in the elongation of mycolic acid chain. The importance of mycolic acid for Mtb makes all the enzymes in this synthesis pathway potential drug targets including HadAB and HadBC. In fact, they were exact downstream enzymes of InhA, an approved target of currently first-line drug isoniazid. So far as we know, there are no crystal structures of HadAB and HadBC reported and the knowledge of catalytic mechanism is unclear as well. Thus, our research will fill in these gaps by deepening our understanding of it enzymatic catalysis from molecular perspective. Our research also aims to unveil inhibition mechanisms by studying the complex structures of HadABC with either flavonoid inhibitors or anti-TB drugs Isoxyl and Thiacetazone, which will lay sound structural basis and provide important clues for the anti-TB drug development.", "\u8d1f\u8d23\u4eba\u804c\u79f0": "\u526f\u7814\u7a76\u5458"}, {"\u9879\u76ee\u540d\u79f0": "\u5355\u9897\u7c92\u4f4e\u6e29\u900f\u5c04\u7535\u955c\u9ad8\u5206\u8fa8\u7387\u6570\u636e\u6536\u96c6\u7528\u652f\u6301\u819c\u7684\u7814\u7a76", "\u6279\u51c6\u53f7": "31500608", "\u9879\u76ee\u7c7b\u522b": "\u9752\u5e74\u79d1\u5b66\u57fa\u91d1\u9879\u76ee", "\u4f9d\u6258\u5355\u4f4d": "\u4e2d\u56fd\u79d1\u5b66\u9662\u751f\u7269\u7269\u7406\u7814\u7a76\u6240", "\u9879\u76ee\u8d1f\u8d23\u4eba": "\u9ec4\u5c0f\u4fca", "\u8d44\u52a9\u7ecf\u8d39(\u4e07\u5143)": "20", "\u6279\u51c6\u5e74\u5ea6": "2015", "\u5173\u952e\u8bcd": "\u51b7\u51bb\u7535\u955c\u6210\u50cf\u6280\u672f\uff1b\u5355\u9897\u7c92\u4e09\u7ef4\u91cd\u6784\uff1b\u5355\u9897\u7c92\u51b7\u51bb\u7535\u955c\u6cd5", "\u662f\u5426\u7ed3\u9898": "\u662f", "\u7814\u7a76\u6210\u679c(\u671f\u520a\u8bba\u6587;\u4f1a\u8bae\u8bba\u6587;\u8457\u4f5c;\u5956\u52b1;\u4e13\u5229)": "0;0;0;0;2", "\u4f9d\u6258\u5355\u4f4dID": "100067", "\u9879\u76ee\u8d1f\u8d23\u4ebaID": "100172851", "\u9879\u76ee\u7c7b\u522b\u4ee3\u7801": "630", "\u7533\u8bf7\u4ee3\u7801": "C050101", "\u8d77\u6b62\u5e74\u6708": "2016-01\u81f32018-12", "\u4e2d\u6587\u6458\u8981": "\u5355\u9897\u7c92\u4f4e\u6e29\u900f\u5c04\u7535\u955c\u6280\u672f\u53d1\u5c55\u81f3\u4eca\uff0c\u6700\u5927\u7684\u74f6\u9888\u5728\u4e8e\u6837\u54c1\u5236\u5907\u3002\u800c\u6837\u54c1\u5236\u5907\u4e0d\u53ef\u6216\u7f3a\u7684\u8017\u6750\u662f\u900f\u5c04\u7535\u955c\u8f7d\u7f51\u3002\u900f\u5c04\u7535\u955c\u8f7d\u7f51\uff08\u7279\u522b\u662f\u8986\u5728\u5176\u4e0a\u7684\u652f\u6301\u819c\uff09\u7684\u4eb2\u6c34\u6027\u80fd\uff0c\u673a\u68b0\u6027\u80fd\uff0c\u5bfc\u7535\u6027\u80fd\u7b49\u76f4\u63a5\u5f71\u54cd\u7740\u5236\u5907\u6837\u54c1\u7684\u8d28\u91cf\u53ca\u6570\u636e\u6536\u96c6\u6548\u7387\u3002\u672c\u9879\u76ee\u5728\u5df2\u81ea\u4e3b\u7814\u5236\u5e76\u5e94\u7528\u7684GIG\u5fae\u9635\u5217\u78b3\u652f\u6301\u819c\u7684\u57fa\u7840\u4e0a\uff0c\u7ee7\u7eed\u7814\u53d1\u66f4\u7b26\u5408\u5b9e\u9645\u9700\u8981\u7684\u7279\u5b9a\u539a\u5ea6\u3001\u5b54\u5f84\u53ca\u5b54\u95f4\u8ddd\u7684\u5fae\u9635\u5217\u652f\u6301\u819c\uff0c\u5e76\u4ee5\u63d0\u5347\u652f\u6301\u819c\u7684\u5bfc\u7535\u6027\u4e3a\u76ee\u6807\u4ee5\u5f00\u53d1\u51fa\u7b2c\u4e8c\u4ee3\u7684\u8be5\u7cfb\u5217\u5fae\u9635\u5217\u652f\u6301\u819c\u3002\u6700\u7ec8\u5c06\u7b2c\u4e8c\u4ee3\u7684\u5fae\u9635\u5217\u652f\u6301\u819c\u5e94\u7528\u5230\u4f4e\u6e29\u900f\u5c04\u7535\u955c\u6280\u672f\u4e2d\uff0c\u964d\u4f4e\u7535\u5b50\u675f\u5f15\u53d1\u7684\u56fe\u50cf\u6f02\u79fb\u72b6\u51b5\uff0c\u63d0\u5347\u5355\u9897\u7c92\u4f4e\u6e29\u900f\u5c04\u7535\u955c\u6210\u50cf\u8d28\u91cf\u548c\u6570\u636e\u6536\u96c6\u6548\u7387\u3002", "\u82f1\u6587\u6458\u8981": "Single particle cryo electron microscopy develops very fast these years. The bottle neck of this technique is at sample preparation. Among all those important factors of sample preparation, e.g. protein purity, concentration, rigidity et al., the properties of TEM grid, to be specific, the properties of supporting film on the TEM grid, is essential to preparing a good cryo sample. Hydrophilicity, strong mechanical strength, high conductivity of the supporting film affect the quality of prepared cryo sample and the efficiency of data collection. Based on the self-developed amorphous carbon film with fixed-pattern micro array (brand name GIG), this study aims to develop more suitable supporting films for cryoTEM usage. It includes designing suitable film thickness, hole size, spacing between hole which leads to high efficiency data collection, and increasing the conductivity of the supporting film at liquid nitrogen temperature which reduces the beam induce movement and enhances the quality of cryoEM images.", "\u8d1f\u8d23\u4eba\u804c\u79f0": "\u9ad8\u7ea7\u5de5\u7a0b\u5e08"}, {"\u9879\u76ee\u540d\u79f0": "\u5e72\u6270\u7d20\u8bf1\u5bfc\u86cb\u767dIFIT/ISG56\u5bb6\u65cf\u6297\u75c5\u6bd2\u529f\u80fd\u7684\u7ed3\u6784\u751f\u7269\u5b66\u7814\u7a76", "\u6279\u51c6\u53f7": "31500609", "\u9879\u76ee\u7c7b\u522b": "\u9752\u5e74\u79d1\u5b66\u57fa\u91d1\u9879\u76ee", "\u4f9d\u6258\u5355\u4f4d": "\u4e2d\u56fd\u79d1\u5b66\u9662\u751f\u7269\u7269\u7406\u7814\u7a76\u6240", "\u9879\u76ee\u8d1f\u8d23\u4eba": "\u51af\u5cf0", "\u8d44\u52a9\u7ecf\u8d39(\u4e07\u5143)": "20", "\u6279\u51c6\u5e74\u5ea6": "2015", "\u5173\u952e\u8bcd": "IFIT/ISG56\u5bb6\u65cf\u86cb\u767d\uff1b\u6297\u75c5\u6bd2\uff1b\u5929\u7136\u514d\u75ab", "\u662f\u5426\u7ed3\u9898": "\u662f", "\u7814\u7a76\u6210\u679c(\u671f\u520a\u8bba\u6587;\u4f1a\u8bae\u8bba\u6587;\u8457\u4f5c;\u5956\u52b1;\u4e13\u5229)": "1;0;0;0;0", "\u4f9d\u6258\u5355\u4f4dID": "100067", "\u9879\u76ee\u8d1f\u8d23\u4ebaID": "100218232", "\u9879\u76ee\u7c7b\u522b\u4ee3\u7801": "630", "\u7533\u8bf7\u4ee3\u7801": "C050101", "\u8d77\u6b62\u5e74\u6708": "2016-01\u81f32018-12", "\u4e2d\u6587\u6458\u8981": "\u75c5\u539f\u4f53\u548c\u5e72\u6270\u7d20\u80fd\u591f\u8bf1\u5bfcISG56/IFIT \u5bb6\u65cf\u86cb\u767d\u7684\u8868\u8fbe, \u5b83\u4eec\u4e0d\u4ec5\u5177\u6709\u6297\u75c5\u6bd2\u4f5c\u7528\uff0c\u800c\u4e14\u8fd8\u53c2\u4e0e\u8c03\u8282\u7ec6\u80de\u7684\u514d\u75ab\u53cd\u5e94\u3002\u524d\u671f\u6211\u4eec\u5728\u56fd\u9645\u4e0a\u7387\u5148\u89e3\u6790\u4e86\u8be5\u5bb6\u65cf\u6210\u5458\u7684\u6676\u4f53\u7ed3\u6784\uff0c\u5e76\u4e14\u901a\u8fc7\u7ed3\u6784\u4fe1\u606f\u8bc1\u5b9e\u4e86\u5176\u6297\u75c5\u6bd2\u529f\u80fd\u4e0e\u6838\u9178\u7ed3\u5408\u80fd\u529b\u6709\u5173\uff0c\u4f46\u662f\u5176\u80cc\u540e\u7684\u5206\u5b50\u673a\u5236\u5c1a\u4e0d\u660e\u786e\u3002\u672c\u9879\u76ee\u62df\u901a\u8fc7\u7ed3\u6784\u751f\u7269\u5b66\u7ed3\u5408\u7ec6\u80de\u751f\u7269\u5b66\u7684\u624b\u6bb5\uff0c\u5728\u5df2\u83b7\u5f97\u7684\u7814\u7a76\u7ed3\u679c\u57fa\u7840\u4e0a\u7cfb\u7edf\u5730\u5f00\u5c55ISG56/IFIT \u5bb6\u65cf\u5404\u4e2a\u6210\u5458\u7684\u6297\u75c5\u6bd2\u548c\u514d\u75ab\u529f\u80fd\u7684\u5206\u5b50\u673a\u5236\u7684\u7814\u7a76\uff0c\u5305\u62ec\u6bd4\u8f83\u5bb6\u65cf\u6210\u5458\u4e4b\u95f4\u7684\u6676\u4f53\u7ed3\u6784\u5dee\u5f02\uff1b\u660e\u786e\u8bc6\u522b\u548c\u7ed3\u5408\u6838\u9178\u7684\u5e8f\u5217\u548c\u7ed3\u6784\u7684\u7279\u5f02\u6027\uff1b\u68c0\u6d4b\u5728\u514d\u75ab\u53cd\u5e94\u4fe1\u53f7\u901a\u8def\u4e2d\u76f8\u4e92\u4f5c\u7528\u7684\u5206\u5b50\uff0c\u6700\u7ec8\u63ed\u793a\u5bb6\u65cf\u5404\u6210\u5458\u9009\u62e9\u6027\u6fc0\u6d3b\u8868\u8fbe\u7684\u6761\u4ef6\u548c\u7279\u5f02\u6027\u6297\u75c5\u6bd2\u7684\u539f\u56e0\u3002\u672c\u9879\u76ee\u7684\u7814\u7a76\u6210\u679c\u5c06\u5bf9\u5bbf\u4e3b\u6297\u75c5\u6bd2\u5929\u7136\u514d\u75ab\u9886\u57df\u7684\u7814\u7a76\u4ee5\u53ca\u76f8\u5e94\u7684\u514d\u75ab\u4e34\u5e8a\u6cbb\u7597\u5177\u6709\u91cd\u8981\u7684\u7406\u8bba\u548c\u73b0\u5b9e\u610f\u4e49\u3002", "\u82f1\u6587\u6458\u8981": "ISG56/IFIT family proteins\uff0cwhich be induced by interferon and pathogen\uff0chave antiviral functions and can regulate cellular immune response. Previously, we first solved the crystal structure of ISG56/IFIT family proteins and discovered that their antiviral functions are related to their ability to recognize nucleotides. However, the molecular mechanism remains unknown. In this project, we aim to reveal the mechanism of ISG56/IFIT proteins using structural and cellular biology methods. Base on the information on crystal structure differences, nucleic acid recognitions, binding partners in innate immune pathway, we try to propose the mechanism of specificity of ISG56/IFIT family proteins' antiviral functions. Our results will deepen people's understanding on innate immune response and provide practical significance on clinical treatment.", "\u8d1f\u8d23\u4eba\u804c\u79f0": "\u535a\u58eb\u540e"}, {"\u9879\u76ee\u540d\u79f0": "Wnt\u4fe1\u53f7\u901a\u8def\u4e2d\u03b2-catenin\u53ca\u5176\u7ec6\u80de\u6838\u5185\u5171\u6fc0\u6d3b\u56e0\u5b50\u590d\u5408\u7269\u7684\u7ed3\u6784\u751f\u7269\u5b66\u7814\u7a76", "\u6279\u51c6\u53f7": "31500610", "\u9879\u76ee\u7c7b\u522b": "\u9752\u5e74\u79d1\u5b66\u57fa\u91d1\u9879\u76ee", "\u4f9d\u6258\u5355\u4f4d": "\u4e2d\u56fd\u79d1\u5b66\u9662\u751f\u7269\u7269\u7406\u7814\u7a76\u6240", "\u9879\u76ee\u8d1f\u8d23\u4eba": "\u5b59\u4f1f", "\u8d44\u52a9\u7ecf\u8d39(\u4e07\u5143)": "20", "\u6279\u51c6\u5e74\u5ea6": "2015", "\u5173\u952e\u8bcd": "\u86cb\u767d\u8d28\uff1b\u76f8\u4e92\u4f5c\u7528\uff1b\u6676\u4f53\u7b5b\u9009\uff1b\u7ed3\u6784\u89e3\u6790\uff1b\u5206\u5b50\u7f6e\u6362", "\u662f\u5426\u7ed3\u9898": "\u662f", "\u7814\u7a76\u6210\u679c(\u671f\u520a\u8bba\u6587;\u4f1a\u8bae\u8bba\u6587;\u8457\u4f5c;\u5956\u52b1;\u4e13\u5229)": "1;0;0;0;0", "\u4f9d\u6258\u5355\u4f4dID": "100067", "\u9879\u76ee\u8d1f\u8d23\u4ebaID": "100045287", "\u9879\u76ee\u7c7b\u522b\u4ee3\u7801": "630", "\u7533\u8bf7\u4ee3\u7801": "C050101", "\u8d77\u6b62\u5e74\u6708": "2016-01\u81f32018-12", "\u4e2d\u6587\u6458\u8981": "Wnt/\u03b2-catenin\u4fe1\u53f7\u901a\u8def\u7684\u8fc7\u5ea6\u6fc0\u6d3b\u4f1a\u5bfc\u81f4\u8bb8\u591a\u764c\u75c7\u7684\u53d1\u751f\u3002\u03b2-catenin\u662f\u8be5\u901a\u8def\u4e0a\u7684\u4e2d\u5fc3\u6548\u5e94\u5206\u5b50\uff0c\u5b83\u7684\u8868\u8fbe\u4e0a\u8c03\u662f\u8fd9\u4e9b\u764c\u75c7\u53d1\u751f\u7684\u9a71\u52a8\u56e0\u7d20\u3002\u5728\u7ec6\u80de\u6838\u5185\uff0c\u591a\u79cd\u5171\u6fc0\u6d3b\u56e0\u5b50\u4e0e\u03b2-catenin\u76f8\u4e92\u4f5c\u7528\uff0c\u5171\u540c\u6fc0\u6d3b\u4e0b\u6e38\u80bf\u7624\u4fc3\u8fdb\u56e0\u5b50\u5982cyclin-D\u548cc-Myc\u7684\u8f6c\u5f55\uff0c\u5176\u4e2dM1\u578b\u53c9\u5934\u6846\u86cb\u767d\uff08FoxM1\uff09\u548cPCNA\u76f8\u5173\u56e0\u5b50\uff08PAF\uff09\u5c31\u662f\u5176\u4e2d\u4e24\u4e2a\u3002FoxM1\u4fc3\u8fdb\u03b2-catenin\u5728\u7ec6\u80de\u6838\u5185\u7684\u5b9a\u4f4d\uff0c\u5e76\u53ef\u4ee5\u4fc3\u8fdbWnt\u5e94\u6fc0\u57fa\u56e0\u7684\u8868\u8fbe\uff0c\u5728\u4eba\u7c7b\u7684\u591a\u79cd\u80bf\u7624\uff08\u6bd4\u5982\u795e\u7ecf\u80f6\u8d28\u7624\uff09\u4e2d\u90fd\u6709\u8fc7\u8868\u8fbe\u3002PAF\u5219\u5728\u7ed3\u76f4\u80a0\u764c\u548c\u80a0\u5e72\u7ec6\u80de\u4e2d\u7279\u5f02\u8868\u8fbe\u3002\u56e0\u4e3a\u03b2-catenin-FoxM1\u548c\u03b2-catenin-PAF\u590d\u5408\u4f53\u7684\u5f62\u6210\u662fWnt/\u03b2-catenin\u4e0b\u6e38\u7684\u91cd\u8981\u4e8b\u4ef6\uff0c\u5bf9\u80bf\u7624\u7684\u53d1\u751f\u53ca\u6076\u5316\u8d77\u91cd\u8981\u4f5c\u7528\uff0c\u6211\u4eec\u8ba1\u5212\u5bf9\u5b83\u4eec\u5f00\u5c55\u7ed3\u6784\u751f\u7269\u5b66\u7814\u7a76\uff0c\u4ee5\u4fbf\u9610\u91ca\u76f8\u5173\u764c\u75c7\u7684\u53d1\u751f\u673a\u7406\uff0c\u5e76\u4e3a\u4eba\u7c7b\u764c\u75c7\u6cbb\u7597\u63d0\u4f9b\u65b0\u7684\u601d\u8def\u3002", "\u82f1\u6587\u6458\u8981": "Hyperactivation of the canonical Wnt/\u03b2-catenin signaling pathway can cause many types of cancers. \u03b2-catenin is the central effector of this signaling pathway, and its upregulation is a driving factor for these cancers. In the nucleus, many coactivators interact with \u03b2-catenin, activating transcription of downstream tumor-promoting factors such as cyclin-D and c-Myc. Forhead box protein M1 type (FoxM1) and PCNA-associated factor (PAF) are two \u03b2-catenin-specific transcriptional coactivators. FoxM1 promotes \u03b2-catenin nuclear localization and induces expression of Wnt responsive genes, and is overexpressed in many cancer types, including glioma. As to PAF, it is specifically expressed in colon cancer and intestine stem cells.  Because formations of \u03b2-catenin-FoxM1 and \u03b2-catenin-PAF complex are critical events downstream of Wnt/\u03b2-catenin signaling pathway, which play vital roles in tumorigenesis and metastasis of many cancers, we embark on investigating the interactions between \u03b2-catenin and FoxM1/PAF employing structural biological methods.  We aim to elucidate the molecular mechanism of tumorigenicity and try to provide novel insights into the therapy of human cancers.", "\u8d1f\u8d23\u4eba\u804c\u79f0": "\u535a\u58eb\u540e"}, {"\u9879\u76ee\u540d\u79f0": "\u5e94\u7528\u7535\u5b50\u987a\u78c1\u5171\u632f\u6280\u672f\u63a2\u7a76\u7ed3\u6838\u5206\u679d\u6746\u83cc\u5206\u6ccc\u7cfb\u7edf\u5185\u819c\u86cb\u767dRv3882c\u8de8\u819c\u7ed3\u6784\u57df\u7684\u7ed3\u6784\u7279\u5f81", "\u6279\u51c6\u53f7": "31500611", "\u9879\u76ee\u7c7b\u522b": "\u9752\u5e74\u79d1\u5b66\u57fa\u91d1\u9879\u76ee", "\u4f9d\u6258\u5355\u4f4d": "\u4e2d\u56fd\u79d1\u5b66\u9662\u5408\u80a5\u7269\u8d28\u79d1\u5b66\u7814\u7a76\u9662", "\u9879\u76ee\u8d1f\u8d23\u4eba": "\u4e8e\u7490", "\u8d44\u52a9\u7ecf\u8d39(\u4e07\u5143)": "20", "\u6279\u51c6\u5e74\u5ea6": "2015", "\u5173\u952e\u8bcd": "\u5206\u679d\u6746\u83cc\u5206\u6ccc\u7cfb\u7edf\uff1b\u819c\u86cb\u767d\uff1b\u4f4d\u70b9\u7279\u5f02\u6027\u81ea\u65cb\u6807\u8bb0\uff1b\u7535\u5b50\u987a\u78c1\u5171\u632f\uff1b\u7ed3\u6784\u6d4b\u5b9a", "\u662f\u5426\u7ed3\u9898": "\u662f", "\u7814\u7a76\u6210\u679c(\u671f\u520a\u8bba\u6587;\u4f1a\u8bae\u8bba\u6587;\u8457\u4f5c;\u5956\u52b1;\u4e13\u5229)": "2;0;0;0;0", "\u4f9d\u6258\u5355\u4f4dID": "100212", "\u9879\u76ee\u8d1f\u8d23\u4ebaID": "100134186", "\u9879\u76ee\u7c7b\u522b\u4ee3\u7801": "630", "\u7533\u8bf7\u4ee3\u7801": "C050101", "\u8d77\u6b62\u5e74\u6708": "2016-01\u81f32018-12", "\u4e2d\u6587\u6458\u8981": "\u7ed3\u6838\u5206\u679d\u6746\u83cc\u7684ESX-1\u5206\u6ccc\u7cfb\u7edf\u80fd\u4f7f\u83cc\u4f53\u5206\u6ccc\u7684\u81f4\u75c5\u56e0\u5b50\u3001\u5b58\u6d3b\u56e0\u5b50\u7b49\u86cb\u767d\u8d28\u7a7f\u8fc7\u5176\u9ad8\u5ea6\u758f\u6c34\u81f4\u5bc6\u7684\u7ec6\u80de\u88ab\u819c\uff0c\u5bf9\u7ed3\u6838\u5206\u679d\u6746\u83cc\u7684\u6bd2\u529b\u548c\u5b58\u6d3b\u6781\u4e3a\u5173\u952e\u3002\u56e0\u6b64\uff0c\u6709\u5173ESX-1\u5206\u6ccc\u7cfb\u7edf\u76f8\u5173\u7ec4\u6210\u86cb\u767d\u7684\u7ed3\u6784\u5206\u6790\u5bf9\u4e8e\u7406\u89e3\u7ed3\u6838\u6746\u83cc\u611f\u67d3\u673a\u5236\u5177\u6709\u975e\u5e38\u91cd\u8981\u7684\u610f\u4e49\u3002Rv3882c\u86cb\u767d\u662fESX-1\u5206\u6ccc\u7cfb\u7edf\u4e2d\u4e00\u79cd\u91cd\u8981\u7684\u5185\u819c\u86cb\u767d\uff0c\u53ef\u80fd\u4e0e\u5176\u4ed6\u7ec4\u6210\u86cb\u767d\u5171\u540c\u5f62\u6210\u901a\u9053\u7c7b\u590d\u5408\u7269\uff0c\u8d1f\u8d23\u8f6c\u8fd0\u5e95\u7269\u7a7f\u8fc7\u7ec6\u80de\u88ab\u819c\uff0c\u4f46\u76ee\u524d\u5176\u7a7a\u95f4\u7ed3\u6784\u548c\u786e\u5207\u7684\u751f\u7269\u5b66\u529f\u80fd\u5c1a\u4e0d\u660e\u786e\uff0c\u4ecd\u4e9f\u5f85\u7814\u7a76\u3002\u672c\u9879\u76ee\u5c06\u7ed3\u5408\u4f4d\u70b9\u7279\u5f02\u6027\u81ea\u65cb\u6807\u8bb0\u4e0e\u7535\u5b50\u987a\u78c1\u5171\u632f\u6280\u672f\uff0c\u901a\u8fc7\u83b7\u53d6Rv3882c\u86cb\u767d\u8de8\u819c\u7ed3\u6784\u57df\u7684\u8fd0\u52a8\u6027\u4fe1\u606f\u3001\u6613\u8d8b\u6027\u4fe1\u606f\u4ee5\u53ca\u5728\u819c\u73af\u5883\u4e2d\u7684\u53d6\u5411\u4fe1\u606f\uff0c\u7efc\u5408\u5206\u6790\u5f97\u5230Rv3882c\u86cb\u767d\u8de8\u819c\u7ed3\u6784\u57df\u5728\u819c\u73af\u5883\u4e2d\u7684\u4e09\u7ef4\u7ed3\u6784\u6a21\u578b\u3002\u672c\u9879\u76ee\u7684\u987a\u5229\u5f00\u5c55\uff0c\u5c06\u4e3aRv3882c\u86cb\u767d\u7684\u7ed3\u6784\u7814\u7a76\u63d0\u4f9b\u91cd\u8981\u4f9d\u636e\uff0c\u6709\u52a9\u4e8e\u8fdb\u4e00\u6b65\u9610\u660e\u7ed3\u6838\u5206\u679d\u6746\u83cc\u7684\u5206\u6ccc\u7cfb\u7edf\u4e0e\u81f4\u75c5\u673a\u5236\uff0c\u4e5f\u4e3a\u5e94\u7528\u7535\u5b50\u987a\u78c1\u5171\u632f\u6280\u672f\u7814\u7a76\u5176\u4ed6\u819c\u86cb\u767d\u7ed3\u6784\u63d0\u4f9b\u65b9\u6cd5\u4e0e\u601d\u8def\u3002", "\u82f1\u6587\u6458\u8981": "The ESX-1 secretion system of Mycobacterium tuberculosis serves to secrete proteins, such as virulence factors and survival factors, across its highly hydrophobic and poorly permeable cell envelop, which is crucial for the virulence and survival of Mycobacterium tuberculosis. Therefore, structural investigation on component proteins of ESX-1 secretion system is very important for understanding the infection mechanisms of Mycobacterium tuberculosis. Rv0082c is a very important membrane protein of ESX-1 secretion system and is located on the inner membrane of Mycobacterium tuberculosis. It was predicted that Rv3382c forms a channel-like complex with other proteins and functions to transport the substrates across the mycobacterial cell envelope. However, the structure and function of this protein is still unclear. In this proposal, we are trying to characterize the structure of the transmembrane domain of membrane protein Rv3882c by combing Site Directed Spin Labelling (SDSL) technology and Electron Paramagnetic Resonance (EPR) spectroscopy. The acquired mobility, accessibility and orientation information in membrane will be integrated to derive a three dimensional structural model of the transmembrane domain of Rv3882c. Successful implementation of this project will not only yield valuable information for structural determination of Rv3882c, but also provide deeper insights of the protein secretion system and pathogenic mechanism of Mycobacterium tuberculosis. Also, this project will provide method of using EPR as the tool for structural studies of other membrane proteins.", "\u8d1f\u8d23\u4eba\u804c\u79f0": "\u526f\u7814\u7a76\u5458"}, {"\u9879\u76ee\u540d\u79f0": "\u771f\u6838\u751f\u7269mRNA\u8f6c\u5f55\u51fa\u6838\u590d\u5408\u7269TREX-1\u7684\u7ed3\u6784\u4e0e\u529f\u80fd\u7814\u7a76", "\u6279\u51c6\u53f7": "31500612", "\u9879\u76ee\u7c7b\u522b": "\u9752\u5e74\u79d1\u5b66\u57fa\u91d1\u9879\u76ee", "\u4f9d\u6258\u5355\u4f4d": "\u8bb8\u660c\u5b66\u9662", "\u9879\u76ee\u8d1f\u8d23\u4eba": "\u82cf\u6d4b\u6d0b", "\u8d44\u52a9\u7ecf\u8d39(\u4e07\u5143)": "20", "\u6279\u51c6\u5e74\u5ea6": "2015", "\u5173\u952e\u8bcd": "mRNA\u8f6c\u5f55\u51fa\u6838\u590d\u5408\u7269\uff1bTHO\u590d\u5408\u7269\uff1b\u86cb\u767d\u8d28\u7ed3\u6784\u751f\u7269\u5b66\uff1bX-\u5c04\u7ebf\u6676\u4f53\u5b66\uff1b\u51b7\u51bb\u7535\u955c", "\u662f\u5426\u7ed3\u9898": "\u662f", "\u7814\u7a76\u6210\u679c(\u671f\u520a\u8bba\u6587;\u4f1a\u8bae\u8bba\u6587;\u8457\u4f5c;\u5956\u52b1;\u4e13\u5229)": "0;0;0;0;0", "\u4f9d\u6258\u5355\u4f4dID": "400411", "\u9879\u76ee\u8d1f\u8d23\u4ebaID": "100181698", "\u9879\u76ee\u7c7b\u522b\u4ee3\u7801": "630", "\u7533\u8bf7\u4ee3\u7801": "C050101", "\u8d77\u6b62\u5e74\u6708": "2016-01\u81f32018-12", "\u4e2d\u6587\u6458\u8981": "\u771f\u6838\u751f\u7269mRNA\u8f6c\u5f55\u51fa\u6838\u590d\u5408\u7269TREX-1\u5e7f\u6cdb\u5b58\u5728\u4e8e\u4ece\u9175\u6bcd\u5230\u54fa\u4e73\u52a8\u7269\u4e2d\uff0c\u53c2\u4e0emRNA\u7684\u8f6c\u5f55\u3001\u8f6c\u5f55\u540e\u52a0\u5de5\u548c\u51fa\u6838\u8fd0\u8f93\u7b49\u4e00\u7cfb\u5217\u8fc7\u7a0b\u3002\u6709\u62a5\u9053\u6307\u51fa\uff0cTREX-1\u590d\u5408\u7269\u7ec4\u5206\u5728\u5f88\u591a\u764c\u75c7\u7ec4\u7ec7\u4e2d\u68c0\u6d4b\u5230\u8868\u8fbe\u5f02\u5e38\u3002TREX-1\u590d\u5408\u7269\u5728\u771f\u6838\u751f\u7269\u4e2d\u4fdd\u5b88\u6027\u8f83\u9ad8\uff0c\u9175\u6bcd\u6e90TREX-1\u590d\u5408\u7269\u7531Sub2\u3001Yra1\u548cTHO\u590d\u5408\u7269\u7ec4\u6210\uff0c\u4eba\u6e90TREX-1\u590d\u5408\u7269\u7531Uap56\u3001Yra1\u4ee5\u53ca\u4eba\u6e90THO\u590d\u5408\u7269\u7ec4\u6210\u3002\u76ee\u524d\uff0c\u7f3a\u4e4fTREX-1\u590d\u5408\u7269\u7684\u9ad8\u5206\u8fa8\u7387\u4e09\u7ef4\u7ed3\u6784\uff0c\u8fd9\u6781\u5927\u7684\u963b\u788d\u4e86\u5bf9\u5176\u53c2\u4e0epre-mRNA\u52a0\u5de5\u5206\u5b50\u673a\u7406\u7684\u6df1\u5165\u7814\u7a76\u3002\u6211\u4eec\u4e4b\u524d\u7684\u7814\u7a76\u901a\u8fc7\u6606\u866b\u6746\u72b6\u75c5\u6bd2\u4f53\u5916\u91cd\u7ec4\u8868\u8fbe\u83b7\u5f97\u4e86\u9ad8\u7eaf\u5ea6\u7684\u9175\u6bcd\u6e90THO\u590d\u5408\u7269\u3002\u5728\u6b64\u57fa\u7840\u4e0a\uff0c\u672c\u9879\u76ee\u62df\u5bf9\u9175\u6bcd\u548c\u4eba\u6e90\u7684TREX-1\u590d\u5408\u7269\u8fdb\u884c\u7ec4\u88c5\u4e0e\u7eaf\u5316\uff0c\u901a\u8fc7\u7ed3\u5408\u86cb\u767d\u8d28X\u5c04\u7ebf\u6676\u4f53\u5b66\u548c\u51b7\u51bb\u7535\u955c\u6280\u672f\uff0c\u4ee5\u671f\u83b7\u5f97TREX-1\u590d\u5408\u7269\u9ad8\u5206\u8fa8\u7387\u4e09\u7ef4\u7ed3\u6784\uff0c\u5e76\u8f85\u4ee5\u751f\u7269\u5316\u5b66\u548c\u7ec6\u80de\u751f\u7269\u5b66\u6280\u672f\uff0c\u7814\u7a76\u5176\u7ec4\u88c5\u53ca\u53c2\u4e0emRNA\u51fa\u6838\u7684\u5206\u5b50\u673a\u5236\u3002", "\u82f1\u6587\u6458\u8981": "Eukaryotic mRNA TRanscription/EXport complex-1 (TREX-1 complex) is evolutionarily conserved multi-protein complex from yeast to human, participating in mRNA transcription, post-transcription processing and export. Previous report indicated that different protein component of TREX-1 complex has dysregulated expressed in different cancer specimens. Yeast TREX-1 complex consists Sub2, Yra1 and THO complex, while human TREX-1 complex consists Uap56 (yeast Sub2 homologous protein), Aly (yeast Yra1 homologous protein) and human THO complex. The detail mechanism of how TREX-1 complex participate pre-mRNA maturation and export is still obscurity, due to the miss of high-resolution 3D structural model of TREX-1 complex. In previous study, we get highly purified yeast THO complex through recombinant baculovirus expression system. Based on these, we try to reconstitute yeast and human TREX-1 complex in vivo and in vitro, through protein X-ray crystallography and cyro-EM technology, aim to get high-resolution 3D structure of TREX-1 complex. We also try to use biochemical and cell biology method to investigate the molecular mechanism of TREX-1 assembling and its participation mRNA export.", "\u8d1f\u8d23\u4eba\u804c\u79f0": "\u8bb2\u5e08"}, {"\u9879\u76ee\u540d\u79f0": "\u4e00\u79cd\u65b0\u7684\u8461\u8404\u7cd6\u8131\u6c22\u9176FAD-GDH\u7684\u6676\u4f53\u7ed3\u6784\u4e0e\u50ac\u5316\u673a\u5236\u7814\u7a76", "\u6279\u51c6\u53f7": "31560244", "\u9879\u76ee\u7c7b\u522b": "\u5730\u533a\u79d1\u5b66\u57fa\u91d1\u9879\u76ee", "\u4f9d\u6258\u5355\u4f4d": "\u9075\u4e49\u533b\u79d1\u5927\u5b66", "\u9879\u76ee\u8d1f\u8d23\u4eba": "\u6768\u6108\u4e30", "\u8d44\u52a9\u7ecf\u8d39(\u4e07\u5143)": "40", "\u6279\u51c6\u5e74\u5ea6": "2015", "\u5173\u952e\u8bcd": "", "\u662f\u5426\u7ed3\u9898": "\u5426", "\u7814\u7a76\u6210\u679c(\u671f\u520a\u8bba\u6587;\u4f1a\u8bae\u8bba\u6587;\u8457\u4f5c;\u5956\u52b1;\u4e13\u5229)": "0;0;0;0;0", "\u4f9d\u6258\u5355\u4f4dID": "", "\u9879\u76ee\u8d1f\u8d23\u4ebaID": "", 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diff --git a/examples/demo.jl b/examples/demo.jl
index d46acce..efbafc5 100644
--- a/examples/demo.jl
+++ b/examples/demo.jl
@@ -1,46 +1,46 @@
-{"h": "", "项目名称": "脱敏态GluA2配体结合域LBD二聚体系综结构及其调控的研究", "批准号": "31500595", "项目类别": "青年科学基金项目", "依托单位": "浙江大学", "项目负责人": "刘主", "资助经费(万元)": "20", "批准年度": "2015", "关键词": "谷氨酸受体；脱敏；顺磁核磁共振；小角X光散射；蛋白质系综结构", "是否结题": "是", "研究成果(期刊论文;会议论文;著作;奖励;专利)": "2;0;0;0;0", "依托单位ID": "100152", "项目负责人ID": "100145756", "项目类别代码": "630", "申请代码": "C050101", "起止年月": "2016-01至2018-12", "中文摘要": "研究蛋白质系综结构及分布比例使我们了解蛋白质如何行使功能。离子型谷氨酸受体2（GluA2）参与脑内重要的生理和病理过程。研究表明，GluA2为二聚—二聚组成的四聚体，其配体结合域（LBD）二聚体结构的变化对GluA2的配体门控至关重要。由于GluA2的LBD二聚作用极弱（KD值约为6mM），因此对其结构研究极少。最近我们实验发现，在脱敏条件下，LBD的瞬态二聚体存在多种构象。为解析脱敏态LBD二聚体原子分辨率的系综结构及分布比例，本项目拟采用化学交联质谱分析的方法获得低分辨率的系综构象和分布，同时运用顺磁弛豫增强的液体核磁共振技术解析原子分辨的系综结构，并联合小角X光散射以计算各构象比例。基于LBD二聚体的结构，我们将突变界面关键位点，结合电生理，阐明全长GluA2脱敏过程与脱敏态LBD二聚体系综结构的构效关系。据此，我们将从脱敏态LBD二聚体结构动态变化的角度揭示GluA2的脱敏机制。", "英文摘要": "Depiction of protein ensemble structure has allowed us to understand how the protein fulfills its function. Ionic glutamate acceptor 2 (GluA2) is involved in many important physiological and pathological processes in the brain. GluA2 is tetrameric (dimer of dimer), and its ligand binding domain (LBD) dimer plays a key role in the ligand gating of GluA2. As the LBD only weakly dimerizes by itself, there has been few studies on the ensemble structure of LBD dimer. We found that the LBD dimer adopts an array of relative orientations as the GluA2 shifts into the desensitized state. We thus propose to determine the ensemble structure of LBD dimer. We will use the CXMS (chemical cross-linking of proteins coupled with mass spectrometry analysis) analysis to obtain a low-resolution picture. Conjointly, we will use PRE (paramagnetic relaxation enhancement) NMR to further characterize the ensemble structure of LBD dimer, and use SAXS (small-angle x-ray scattering) to assess the relative populations of each conformational state. Based on the structural characterization, we will mutate key interfacial residues that may perturb the ensemble structure of LBD dimer, which will be confirmed by electrophysiological analyses. Together, we will illustrate how the structural change of LBD dimer accompanies the desensitization of GluA2. If funded and successfully carried out, the project will provide the structural basis for exquisite pharmacological modulation of GluA2 function.", "负责人职称": "教授"}
-{"h": "", "项目名称": "帕金森病致病蛋白LRRK2的ROC结构域GTP水解抑制机制与结构生物学研究", "批准号": "31500596", "项目类别": "青年科学基金项目", "依托单位": "南京理工大学", "项目负责人": "廖静伶", "资助经费(万元)": "20", "批准年度": "2015", "关键词": "富亮氨酸重复激酶2；ROC结构域；GTP水解活性；结构功能学；帕金森病", "是否结题": "是", "研究成果(期刊论文;会议论文;著作;奖励;专利)": "2;0;0;0;0", "依托单位ID": "100468", "项目负责人ID": "100118874", "项目类别代码": "630", "申请代码": "C050101", "起止年月": "2016-01至2018-12", "中文摘要": "帕金森病是与年龄密切相关的神经退行性疾病之一。LRRK2基因是目前为止突变率最高的帕金森病致病基因，主要表现在LRRK2蛋白激酶活性的异常增高，但其具体生物功能及致病机制仍不明确。深入研究LRRK2蛋白正常生理功能及基因突变的致病机制将为研究帕金森病治疗策略提供分子机制水平的依据。LRRK2蛋白除了具有激酶活性以外，还拥有GTP水解酶活性，该GTP水解酶活性对激酶活性有调节作用，揭示LRRK2蛋白存在分子内调节机制。LRRK2蛋白特有的生化特征使其成为帕金森病非常有希望的治疗靶点。申请者将运用X射线蛋白晶体学，生物化学及生物物理学方法，通过解析LRRK2蛋白中的ROC结构域晶体结构及GTP水解抑制机制来阐明基因突变的致病机理，为新的通过调控GTP水解酶活性来降低LRRK2的激酶活性的方法提供理论依据。", "英文摘要": "Parkinson’s disease (PD) is a devastating neurological condition that ravages people’s quality of life as it progresses from the subtle loss of muscular coordination, to severe physical and mental disability, to eventual death. There is no cure and no available treatments to stop this disease progression. Today, mutations in LRRK2 are the most prevalent known genetic causes of Parkinson’s disease, for both familial and sporadic cases. In spite of the intensive efforts over the past decade, the molecular role of LRRK2 in disease pathogenesis, its function, and the effects of disease-causing mutations remain unknown. Understanding the underlying mechanism of LRRK2 normal function and how it is affected by the disease-associated mutations will reveal novel mechanism-based therapeutic strategies. In addition to LRRK2 being associated with PD and being the most promising drug target for the disease, LRRK2 is an immensely intriguing protein, in that it has two enzymatic activities (GTPase activity and Kinase activity) that, together with other non-enzymatic domains, potentially represent a unique example of an intramolecular signaling system. The concept of the Roc GTPase domain functioning as a molecular switch regulating the overall activity of LRRK2 is conceptually interesting from a biochemical perspective, and it is the key to LRRK2’s normal function and disease process. In addition to the relatively wide prevalence of LRRK2 in PD, it is the most attractive target for drug discovery, because over-activation of its kinase activity is linked to disease pathogenesis, and it is an enzyme with active sites well suited for binding potential drugs. Indeed, LRRK2 kinase activity was effectively inhibited by broad kinase inhibitors that compete for ATP in the ATP-binding pocket. However, their translation into the clinic has been difficult due to adverse effects. Various potential alternative strategies are being considered, including targeting the Roc domain. This proposed study seeks to define the structures of ROC domain and its mutants to understand the GTP hydrolysis mechanism and mutations pathogenesis by using X-ray diffraction crystallography, protein biochemistry and biophysics approaches, which could provide insight into locations on LRRK2 structures that are suitable for mechanism-based drug discovery.", "负责人职称": "副教授"}
-{"h": "", "项目名称": "线性泛素链组装复合物(LUBAC)的调节机制研究", "批准号": "31500597", "项目类别": "青年科学基金项目", "依托单位": "中国科学院上海有机化学研究所", "项目负责人": "刘建平", "资助经费(万元)": "20", "批准年度": "2015", "关键词": "蛋白质复合物；X射线晶体衍射；泛素化；肿瘤坏死因子TNFα；细胞死亡", "是否结题": "是", "研究成果(期刊论文;会议论文;著作;奖励;专利)": "4;0;0;0;0", "依托单位ID": "400014", "项目负责人ID": "100193226", "项目类别代码": "630", "申请代码": "C050101", "起止年月": "2016-01至2018-12", "中文摘要": "线性泛素化是一类广泛参与炎症和先天免疫的新型泛素化修饰。迄今唯一的线性泛素链E3连接酶LUBAC复合物由调节亚基Sharpin、HOIL1和催化亚基HOIP组成。单独的HOIP处于自抑制状态，但可以被Sharpin或HOIL1激活。然而，HOIP的自抑制和激活、与Sharpin的相互作用机制仍然未知。Sharpin缺失小鼠表现出多器官炎症和TNFα通路异常。为了阐明LUBAC复合物的调控机制，本申请计划解析自抑制和激活状态的HOIP催化核心片段，以及Sharpin/HOIP复合物的结构，揭示HOIP的自抑制和激活机制，并设计点突变解除自抑制或者破坏Sharpin对HOIP的激活，研究相应突变体对细胞死亡或RIP1线性泛素化的影响，以检验我们的假说：Sharpin/HOIP复合物对RIP1的线性泛素化决定了TNFα通路的最终效应——炎症或细胞死亡。现有工作进展为实现上述目标奠定了坚实的基础。", "英文摘要": "Linear ubiquitination, a recently discovered novel type of ubiquitination, is extensively involved in numerous signaling pathways related to inflammation and innate immune. Linear ubiquitin chain assembly complex (LUBAC) is the sole identified E3 ubiquitin ligase that catalyzes the formation of linear poly-ubiquitin chain. It consists of two regulatory subunits Sharpin and HOIL1 as well as one catalytic subunit HOIP. The isolated HOIP is in an auto-inhibited state, but it can be activated by Sharpin or HOIL1 to sufficiently promote the linear ubiquitination of target substrates. However, the molecular mechanisms underlying the the auto-inhibition of HOIP, its activation by Sharpin or HOIL1, and the interaction between HOIP and Sharpin are largely unknown. Previous studies indicated that loss of Sharpin in the mouse caused immunodeficiency and multi-organ inflammation, and severely inhibited the linear ubiquitination of TNFα receptor signaling complex. Based on these findings, we propose a hypothesis: the linear ubiquitination level of RIP1 catalyzed by Sharpin/HOIP complex determines the outcome of TNFα signaling—inflammation or cell death. To further understand the regulatory mechanism of LUBAC complex, we aimed to solve the structures of the catalytic fragment of HOIP either in auto-inhibited or in activated states as well as the Sharpin/HOIP complex, thereby to uncover the auto-inhibition and activation mechanism of HOIP. Based on the solved structures, we will design point mutations to specifically disrupt the auto-inhibition or the trans-activation of HOIP mediated by Sharpin; we will further test our hypothesis by assessing the impact of these mutations on the linear ubiquitination level of RIP1 and the TNFα induced cell death. Our current research progress has laid the foundation for us to pursue the scientific goals in this proposal.", "负责人职称": "副研究员"}
-{"h": "", "项目名称": "转录因子CcmR调控蓝细菌碳浓缩机制的结构生物学基础", "批准号": "31500598", "项目类别": "青年科学基金项目", "依托单位": "中国科学技术大学", "项目负责人": "成望", "资助经费(万元)": "20", "批准年度": "2015", "关键词": "蓝藻；碳浓缩机制；转录调控；晶体结构；异构效应", "是否结题": "是", "研究成果(期刊论文;会议论文;著作;奖励;专利)": "1;0;0;0;0", "依托单位ID": "200654", "项目负责人ID": "100047316", "项目类别代码": "630", "申请代码": "C050101", "起止年月": "2016-01至2018-12", "中文摘要": "蓝细菌是被广泛用于光合作用和碳浓缩机制(CO2-concentrating mechanism, CCM)研究的重要模式生物。CcmR是集胞藻PCC6803中的一个调控碳浓缩机制的全局性转录因子，在低碳信号下解除对CCM相关基因的抑制，引起表达上调，促进CO2的吸收，保证光合作用的顺利进行。我们将以CcmR apo-form四聚体晶体结构为基础，综合利用生物信息学、生物化学、分子生物学以及结构生物学手段，对CcmR与DNA和/或信号分子的相互作用及其二元和三元晶体结构进行系统研究，以期揭示CcmR的别构机理，并基于CcmR特异性识别的DNA序列鉴定其调控的下游基因网络。该项目将阐明CcmR的调控碳浓缩机制的结构基础，有望为生态平衡和农业生产提供理论指导。", "英文摘要": "Cyanobacterium is an ideal model for studying the photosynthesis and CO2-concentration mechanism (CCM). The transcriptional factor CcmR was first identified in the cyanobacterium Synechocystis sp. PCC6803. It serves as a global controller to increase the expression of CCM related genes, which are suppressed at a high Ci concentration, thus augmenting the uptake of CO2 for the efficacy photosynthesis. Based on our previously determined crystal structure of the apo-form CcmR tetramer, we will systematically investigate the interactions of CcmR with the putative allosteric molecule and its binding DNA, by combining the methodologies of bioinformatics, biochemistry, molecular biology and structural biology. The findings will enable us to elucidate the CcmR allosteric mechanism, and to identify the gene network under the control of CcmR. This project will provide insights into the CCM regulated by CcmR, and might be helpful for guiding the ecological balance control and agricultural production in the future.", "负责人职称": "博士后"}
-{"h": "", "项目名称": "三维超分辨技术研究细胞核孔复合物的选择性屏障分布", "批准号": "31500599", "项目类别": "青年科学基金项目", "依托单位": "复旦大学", "项目负责人": "马炯", "资助经费(万元)": "21", "批准年度": "2015", "关键词": "细胞核孔复合物；FG屏障；单分子；超分辨显微镜；核孔传输", "是否结题": "是", "研究成果(期刊论文;会议论文;著作;奖励;专利)": "9;0;0;0;0", "依托单位ID": "201361", "项目负责人ID": "100162892", "项目类别代码": "630", "申请代码": "C050101", "起止年月": "2016-01至2018-12", "中文摘要": "细胞核孔复合物（NPC）是真核细胞中连接细胞质和细胞核之间的选择性双向通道。由富含苯丙氨酸-甘氨酸（FG）氨基酸片段的自然非折叠蛋白构成的FG-屏障,选择性地调控基因相关物质,按照被动运输或者主动介入运输的方式进出细胞核。然而，核孔内FG屏障间的相互作用以及分布状况仍然是极具争议的重要科学问题。本项目将基于申请人发明的单点斜入射激发快速超分辨显微镜技术，研究核孔传输蛋白或FG-蛋白片段与FG屏障反应的三维分布图像，从而获得FG-屏障在细胞核孔内完整的分布情况。另外,进一步检测核孔传输蛋白对FG屏障的分布影响，讨论核孔传输的自调控机制。还将从不同传输蛋白或FG-片段在传输过程中的竞争效果，讨论FG屏障对各类基因相关物质传输的优先顺序。最终，完整的三维FG屏障将对核孔蛋白缺失相关的白血病、阿尔兹海默症的致病机制，以及各种类病毒的侵入机制等核孔相关病理机制或基因治疗提供信息。", "英文摘要": "The nuclear pore complexes (NPCs) selectively mediate the bidirectional trafficking of macromolecules between the cytoplasm and the nucleus in eukaryotic cells. The selective barrier formed by natively unfolded phenylalanine-glycine (FG) nucleoporins (Nups) inside the NPC allows for passive and facilitated transport through the NPC. However, the interactions that form the FG-barrier and their spatial distribution in the NPC remain unresolved. Based on the single-point edge-excitation sub-diffusion (SPEED) microscopy techniques, the applicant's invention, three-dimensionally map the interaction distributions between the fluorescent transport receptors (TRs) or FG-fragment and FG barrier. Then, we obtain fully information of the FG-barrier distribution in the NPC. The conformation change of the FG-barrier by TRs would be discussed as self-regulating mechanism of nucleocytoplasmic transport. Also from the competitive effects during different FG-fragments and transport proteins during the transport discuss priorities for the various gene related transport. Finally，the complete three-dimensional FG-barrier distribution will provide information with leukemia, Alzheimer's disease pathogenesis, as well as various types of viruses invade mechanisms for NPC related pathological mechanism or gene therapy.", "负责人职称": "研究员"}
-{"h": "", "项目名称": "成肌细胞融合蛋白myomaker的结构基础与作用机理", "批准号": "31500600", "项目类别": "青年科学基金项目", "依托单位": "清华大学", "项目负责人": "龚德顺", "资助经费(万元)": "9", "批准年度": "2015", "关键词": "膜蛋白；均一性；晶体筛选；结构解析；晶体结构", "是否结题": "是", "研究成果(期刊论文;会议论文;著作;奖励;专利)": "0;0;0;0;0", "依托单位ID": "201260", "项目负责人ID": "100177698", "项目类别代码": "630", "申请代码": "C050101", "起止年月": "2016-01至2016-12", "中文摘要": "Myomaker是新发现的一种可以直接调控成肌细胞融合和肌肉再生的蛋白，这是哺乳动物细胞中唯一一个被鉴定的肌肉特异性的调节蛋白。它促进成肌细胞融合以及肌肉再生的活性为受伤后的肌肉再生提供了新的机会，为肌肉性疾病的治疗提供了新的思路。然而，目前对其发挥功能的分子机理仍然一无所知。本项目拟从结构生物学的角度出发，解析其晶体结构，揭示其分子作用机理。", "英文摘要": "Myomaker, a new discovered myoblast fusion activator, which is the only identified muscle-specific protein that directly regulates myoblast fusion and muscle regeneration in mammals. These activities of myomaker provide new opportunities for muscle regeneration and new strategies for therapy of muscle diseases. However, the molecular mechanism of myomaker is still in the dark. The aim of this project is to determinate the crystal structure of myomaker and provide new insights into the functional mechanism of myomaker.", "负责人职称": "博士后"}
-{"h": "", "项目名称": "布氏锥虫中参与基因转录调控的PAF1复合物的结构和功能研究", "批准号": "31500601", "项目类别": "青年科学基金项目", "依托单位": "中国科学技术大学", "项目负责人": "廖善晖", "资助经费(万元)": "20", "批准年度": "2015", "关键词": "PAF1复合物；转录调控；布氏锥虫；蛋白质结构；蛋白质相互作用", "是否结题": "是", "研究成果(期刊论文;会议论文;著作;奖励;专利)": "11;0;0;0;1", "依托单位ID": "200654", "项目负责人ID": "100186764", "项目类别代码": "630", "申请代码": "C050101", "起止年月": "2016-01至2018-12", "中文摘要": "真核生物基因转录的调控在时间和空间上都具有很高的复杂度，细胞内基因转录调节的异常与各类疾病密切相关。在研究转录调节的过程中，大量RNA聚合酶相关蛋白复合体被报道，其中PAF1复合物（RNA polymerase II associated factor complex, PAF1C）就是最近发现的一种。PAF1复合物含有至少 5个不同的蛋白亚基，能够协同其他的转录因子及组蛋白修饰酶来调控转录过程。锥虫是一类单细胞真核原生生物，能够引起多种锥虫病。目前在布氏锥虫属中发现的PAF1复合体组成与高等真核生物不完全保守，可能暗示了布氏锥虫特有的基因转录调节方式。本项研究将结合结构生物学和细胞生物学方法，研究布氏锥虫中PAF1复合物的结构及其在基因转录调控中的作用。本研究不仅将丰富我们对布氏锥虫PAF1复合物和基因转录调控的认识，对于我们了解真核生物PAF1复合物和基因转录调控的进化也具有重要意义。", "英文摘要": "Eukaryotic gene transcription regulation is extremely complex in space and time. Any defect of transcription process is closely related to a variety of diseases. Many protein complexes have been reported during the study of transcription regulation, PAF1C (RNA polymerase II associated factor 1 complex) is such a complex discovered recently. PAF1C, contains at least 5 subunits. It participates in gene transcription regulation cooperatively with other transcription factors and histone modification enzymes. Trypanosomatids, the causative pathogens of trypanosomiasis, are a group of unicellular protozoa. The compositions of PAF1C of Trypanosoma brucei (T. brucei) is not fully conserved with that from higher eukaryotes, which may imply species-specific regulation pathway of gene transcription. Here, we are trying to explore the structure of PAF1C and its role in gene transcription regulation in T. brucei, by combining the techniques of structural biology and cell biology. This study will not only enrich our knowledge of PAF1C’s role in transcription regulation in T. brucei, but also has important implications for our understanding of the evolution of eukaryotic PAF1 complex and gene transcription regulation.", "负责人职称": "副研究员"}
-{"h": "", "项目名称": "铜绿微囊藻气囊蛋白的结构和功能研究", "批准号": "31500602", "项目类别": "青年科学基金项目", "依托单位": "中国科学技术大学", "项目负责人": "代亚男", "资助经费(万元)": "20", "批准年度": "2015", "关键词": "铜绿微囊藻；气囊；气囊蛋白；晶体结构；结构蛋白", "是否结题": "是", "研究成果(期刊论文;会议论文;著作;奖励;专利)": "0;0;0;0;0", "依托单位ID": "200654", "项目负责人ID": "100047317", "项目类别代码": "630", "申请代码": "C050101", "起止年月": "2016-01至2018-12", "中文摘要": "铜绿微囊藻是一种单细胞浮游蓝藻，能大量产生气囊，营养丰富时在淡水水体表面聚集暴发水华。气囊是一种完全由蛋白质组成的中空、充满气体的惰性结构。气囊为藻细胞提供浮力，使其自行调节在自然水体中的垂直位置，漂浮到氧气和光照都适宜的位置以利于自身生长和生境殖民化。气囊不仅是铜绿微囊藻能成为优势藻种的重要原因之一，也在水华的暴发过程中起到了调节作用。然而，人们至今尚未弄清气囊的结构及其合成降解机制。为了探究气囊合成相关蛋白的三维结构，进一步重构气囊这一中空结构的三维面貌，我们以铜绿微囊藻Microcystis aeruginosa PCC 7806中的气囊合成相关的一组Gvp蛋白为研究对象，利用X射线晶体学手段解析各个气囊蛋白的结构，并联合运用高分辨率冷冻电镜，蛋白质免疫印迹法和胶体金标记等方法来分析各结构蛋白的具体定位。该项目将解析气囊原子分辨率水平上的三维结构，对治理水华暴发有一定理论指导意义。", "英文摘要": "Microcystis aeruginosa was investigated and identified as a planktonic unicellular cyanobacterium which is responsible for algal bloom in the freshwater environments. In Microcystis cells, an abundant production of intracellular structures, the gas vesicle, an inert, hollow and gas-filled structure, formed solely from proteins, provides cells with buoyancy and regulates their vertical distribution in natural waters. Cyanobacteria could float taxis toward air-liquid interfaces of water environments, positioning themselves at a depth with optimal light and oxygen supply for better growth, subsequent niche colonization and water-bloom formation. However, the fine structure of gas vesicle and its  biosynthesis/degradation mechanisms are still unclear. To determine three dimensional structures of gas vesicle proteins and remodeling the integral hollow structure, we are committed to solve structures of Gvp proteins from Microcystis aeruginosa PCC 7806 using X-ray crystallography. Moreover, in combination with high-resolution cryo-electron microscopy, we will investigate the localization of individual Gvp proteins by immunoblotting and immunogold labeling-based tomography. These findings will provide insights into structural characteristics of gas vesicle and the rational control of algal bloom.", "负责人职称": "博士后"}
-{"h": "", "项目名称": "膜环境对膜蛋白DAGK结构与功能的影响", "批准号": "31500603", "项目类别": "青年科学基金项目", "依托单位": "中国科学院武汉物理与数学研究所", "项目负责人": "陈艳可", "资助经费(万元)": "20", "批准年度": "2015", "关键词": "膜蛋白结构；固体核磁共振；天然膜；去垢剂；甘油二脂激酶", "是否结题": "是", "研究成果(期刊论文;会议论文;著作;奖励;专利)": "3;0;0;0;0", "依托单位ID": "201322", "项目负责人ID": "100150871", "项目类别代码": "630", "申请代码": "C050101", "起止年月": "2016-01至2018-12", "中文摘要": "膜蛋白的结构与功能深受所处环境的影响。目前，在PDB数据库中收录的膜蛋白结构90%以上是在膜模拟环境—去垢剂胶束中解析的。然而，在去垢剂的环境中，膜蛋白的真实结构能否被维持是备受结构生物学家关注的问题。大肠杆菌甘油二脂激酶(DAGK)是一个很重要的三跨膜蛋白，其三维结构已经被液体核磁共振和X-Ray晶体衍射的方法在去垢剂胶束或脂质立方相中所解析，然而由于环境的不同，得到的结构差别很大，并且这两种结构都不是在DAGK的天然膜环境中进行解析的。固体核磁共振技术可以在接近膜蛋白天然环境的磷脂双层膜中解析其三维结构，是测定与证实膜蛋白结构的有力工具。本项目拟采用固体核磁共振技术在大肠杆菌磷脂膜的环境下对DAGK的三维结构进行解析，并分析不同环境下DAGK活性区域的结构变化，阐释膜蛋白结构与功能对膜环境的依赖性。", "英文摘要": "The structures of membrane proteins are profoundly influenced by membrane–protein interactions. To date, more than 90% structures of membrane protein in the PDB have been determined in membrane mimetic environments-detergent micelles. However, it is very difficult to obtain membrane mimetic environments that support the native structure and function of a membrane protein. Escherichia coli diacylglycerol kinase (DAGK) is a very important transmembrane protein of which three dimensional structure has been determined in detergent micelles or lipid cubic phase by solution-state NMR or X-Ray crystallography. Due to the different membrane mimetic environments, the two structures differ obviously. Solid-state NMR is a powerful tool for studying structures of membrane proteins in the native-like membrane environments. This project aims to use Solid-state NMR to determin the sturcture of DAGK in Escherichia coli total lipids bilayer. Then, we will expain the influence of membrane environments on membrane protein structure and function by comparation the structures of DAGK active domain in different membrane environments.", "负责人职称": "助理研究员"}
-{"h": "", "项目名称": "与ALS/FTD相关联的C9orf72六核苷酸重复扩增形成G-四链体的结构研究", "批准号": "31500604", "项目类别": "青年科学基金项目", "依托单位": "香港科技大学深圳研究院", "项目负责人": "周波", "资助经费(万元)": "20", "批准年度": "2015", "关键词": "核磁共振；G-四链体；C9orf72六核苷酸重复扩增；肌萎缩性侧索硬化症；额颞叶痴呆", "是否结题": "是", "研究成果(期刊论文;会议论文;著作;奖励;专利)": "2;0;0;0;0", "依托单位ID": "404024", "项目负责人ID": "100175543", "项目类别代码": "630", "申请代码": "C050101", "起止年月": "2016-01至2018-12", "中文摘要": "肌萎缩性侧索硬化症（ALS）和额颞叶痴呆（FTD）是严重的神经退行性疾病。在家族性或散发性ALS/FTD患者中，位于9号染色体第72个开放阅读框基因（C9orf72）的GGGGCC六核苷酸重复扩增（HRE）是最常见的遗传致病因子。以往研究表明，C9orf72 HRE无论是作为DNA或转录的RNA产物，均可折叠成具有不同结构的G-四链体，并与ALS/FTD的致病机理密切相关。由于缺乏相关G-四链体的高分辨率结构信息，C9orf72 HRE形成G-四链体的分子机理仍不清楚。本研究将利用核磁共振技术首次获取C9orf72 HRE DNA及RNA G-四链体的高分辨率结构，对于在ALS/FTD患者中由于此种结构导致的异常转录产物诱发疾病的分子机理提供极有价值的信息，并且为针对C9orf72 HRE G-四链体设计小分子用以靶向调节ALS/ FTD的发病机制奠定必要的结构学基础。", "英文摘要": "Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are devastating neurological diseases. Abnormal expansion of a hexanucleotide repeat, (GGGGCC)n, is the most common genetic cause of familial and sporadic forms of ALS and FTD. This nucleotide repeat element is located in a non-protein-coding region of the C9orf72 gene. Previous studies suggested that the C9orf72 hexanucleotide repeat expansion (HRE), either as DNA or the transcribed RNA, can fold into G-quadruplexes with distinct structures. It could also form transcriptionally induced RNA-DNA hybrids known as R-loops. These structural polymorphisms lead to C9orf72 HRE-containing abortive transcripts, which may aggregate and form RNA foci in patient cells. Despite the critical connection of C9orf72 HRE G-quadruplexes to the pathogenic mechanism of C9orf72 HRE-linked ALS/FTD, the molecular basis of G-quadruplex formation by C9orf72 HRE remains elusive..In this project, we plan to perform systematic biochemical and structural characterizations for C9orf72 HRE G-quadruplexes. First, we will determine the 3D structure of G-quadruplex formed by the C9orf72 HRE DNA. In our preliminary study, we successfully obtained a homogenous DNA sample, d(GGGGCC)4, which favored a monomeric G-quadruplex fold. We have determined the topology of this G-quadruplex DNA using the nuclear magnetic resonance (NMR) approach. It forms a chair-type G-quadruplex with a four-layer antiparallel G-tetra core and three edgewise loops, which is distinct from known structures of chair-type G-quadruplexes. We will further resolve its detailed structure using NMR techniques. We have also successfully obtained a homogeneous C9orf72 HRE RNA sample with sufficient quality for NMR structure determination. Unlike the monomeric d(GGGGCC)4 DNA, this RNA, r(GGGGCC)GGGG, is an asymmetric dimer. We will perform more NMR studies to obtain its 3D structure. As no structure of the C9orf72 HRE G-quadruplex has ever been solved, the structural information of C9orf72 HRE DNA/RNA G-quadruplexes to be obtained in the current project will provide valuable insights into the molecular mechanism of abortive transcripts formation by C9orf72 HRE and RNA foci appearance in ALS/FTD patients. The outcome of the proposed research will not only provide insight into the molecular mechanism underlying the C9orf72 HRE G-quadruplex formation in the etiology of ALS/FTD, but may also lay the necessary basis for designing small molecules that therapeutically target C9orf72 HRE G-quadruplexes for the modulation of ALS/FTD pathogenesis.", "负责人职称": "副研究员"}
-{"h": "", "项目名称": "Sema-Plexin信号通路中FARP2的结构与功能研究", "批准号": "31500605", "项目类别": "青年科学基金项目", "依托单位": "华中科技大学", "项目负责人": "贺晓静", "资助经费(万元)": "21", "批准年度": "2015", "关键词": "蛋白质结构；相互作用；轴突导向", "是否结题": "是", "研究成果(期刊论文;会议论文;著作;奖励;专利)": "2;0;0;0;0", "依托单位ID": "100113", "项目负责人ID": "100154722", "项目类别代码": "630", "申请代码": "C050101", "起止年月": "2016-01至2018-12", "中文摘要": "神经系统的精确发育发展离不开轴突导向。神经细胞生长椎上的受体接受环境中的轴突导向因子传递的信号，经过一系列蛋白的传递，最后作用于细胞骨架蛋白，从而影响生长椎的走向。Semaphorin-Plexin 通路是其中重要的信号通路之一，我们的研究重点是这一通路中plexin的下游互作蛋白FARP2。FARP2 N端的FERM结构域介导它与Plexin之间的相互作用，但是二者之间的互作模式与分子机制还不清楚。本项目将利用晶体生物学，生物化学，细胞生物学等手段，在结构与功能上研究FARP2及其与Plexin的互作关系和分子调控机制，为进一步理解Sema-Plexin通路下游信号传导机制提供分子依据。我们之前的结构生物学研究发现FARP2 的DH-PH-PH结构域是一种以自我抑制构象存在的小GTP酶的鸟核苷酸交换因子(GEF)，本项目将进一步探讨如何激活FARP2的GEF活性。", "英文摘要": "英文摘要.The correct wiring of the nervous system relies on the precise axon guidance. During development of the nervous system, axons are guided to their proper targets by sensing a variety of extracellular cues in the local environment. The receptor protein on the neuronal growth cones which is located at the tip of the growing axon, recognizes guidance cues. The signal finally selectively alters the stability of the actin cytoskeleton and microtubules that determine the rate and direction  of   axon  extension.  Semaphorin-Plexin  is  one  of  the  classic ligand/receptor systems involved in this process， and we will focus on FARP2, which is a downstream partner of Plexin A1. FARP2 interacts with Plexin A1 though its N terminal FERM domain, but how they bind is still not clear. We are using  the  combination  of  protein  X-ray  crystallography,  biochemical techniques and cell based assay to study the structure and function of FARP2 and its interaction and regulation with Plexin A1. Our research will help us to understand the molecular regulation mechanisms of downstream signal transduction of Sema-plexin pathway.  C terminal domain DH-PH-PH of FARP2 is an auto-inhibited Guanine nucleotide exchange factor (GEF) based on our previous studies, and we will study how to active GEF activity further.", "负责人职称": "教授"}
-{"h": "", "项目名称": "Tip49a/Tip49b及其相关复合物的冷冻电镜结构研究", "批准号": "31500606", "项目类别": "青年科学基金项目", "依托单位": "德州学院", "项目负责人": "宋峰", "资助经费(万元)": "20", "批准年度": "2015", "关键词": "冷冻电镜；单颗粒三维重构；蛋白复合物组装", "是否结题": "是", "研究成果(期刊论文;会议论文;著作;奖励;专利)": "4;0;0;0;0", "依托单位ID": "400969", "项目负责人ID": "100181269", "项目类别代码": "630", "申请代码": "C050101", "起止年月": "2016-01至2018-12", "中文摘要": "Tip49a和Tip49b是AAA+超家族的两个蛋白，它们保守地存在于从酵母到人的多个物种中，在细胞内通常以复合物的形式存在。它们在DNA损伤修复、转录调控、snoRNP成熟、染色质重塑等生命活动中发挥重要的调控作用，但迄今为止仍然没有Tip49a/Tip49b全长蛋白相关复合物的结构报道。本研究拟主要应用冷冻电镜单颗粒三维重构技术解析人源Tip49a/Tip49b及其参与形成的两种高级复合物（R2TP、Tip49a/Tip49b-核小体）的高精度三维结构，并结合生化实验确定Tip49a/Tip49b在两种高级复合物中的作用。本项目的研究成果将为理解Tip49a/Tip49b在snoRNP组装（R2TP复合物）和ATP依赖的染色质重塑（Tip49a/Tip49b-核小体复合物）中的工作机制提供可靠的结构信息。", "英文摘要": "Tip49a and Tip49b are two structurally and functionally highly related proteins that belong to the AAA+ (ATPase Associated with diverse cellular Activities) superfamily. They are existed in many species of which ranging from yeast to human. Both Tip49a and Tip49b are conserved components of various multi-subunit complexes, which are linked to a wide range of cellular processes, such as DNA damage response, transcription regulation, snoRNP biogenesis and ATP-dependent chromatin remodeling. Despite their diverse roles, there is no available high resolution structure of full-length Tip49a/Tip49b protein complex. The mainly purpose of our research is to reveal the high resolution structures of dodecameric Tip49a/Tip49b and determine their functions in two larger complexes which containing them, R2TP and Tip49a/Tip49b-nucleosome complex, by using cryo-EM single particle analysis combining with biochemical and biophysical techniques. Our research will provide insights into the structural basis of Tip49a/Tip49b in mediating snoRNP biogenesis(R2TP complex) and ATP-dependent chromatin remodeling(Tip49a/Tip49b-nucleosome complex).", "负责人职称": "教授"}
-{"h": "", "项目名称": "结核分枝杆菌分枝菌酸合成途径脱水酶HadABC复合物与多种抗结核抑制剂的结构和功能研究", "批准号": "31500607", "项目类别": "青年科学基金项目", "依托单位": "中国科学院上海生命科学研究院", "项目负责人": "李俊", "资助经费(万元)": "20", "批准年度": "2015", "关键词": "结核分枝杆菌；晶体结构；分枝菌酸；脱水酶；药物靶点", "是否结题": "是", "研究成果(期刊论文;会议论文;著作;奖励;专利)": "3;0;0;0;0", "依托单位ID": "201022", "项目负责人ID": "100175031", "项目类别代码": "630", "申请代码": "C050101", "起止年月": "2016-01至2018-12", "中文摘要": "结核病是目前世界上致死率最高、传播范围最广的细菌性疾病。结核分枝杆菌是引发结核病的病原菌，由于耐多药菌株（MDR-TB）和广泛耐药菌株（XDR-TB）的出现，使得现有药物的治疗几乎失效。因此，寻找新的药物靶点以及研究全新作用机制的强力抗结核药物已经成为迫在眉睫的重要任务。由致密的分枝菌酸层构成的细胞壁使得结核分枝杆菌可以逃避免疫攻击和有害物质入侵从而能够存活。脱氢酶HadAB和HadBC是II型分枝菌酸脂链延伸系统（FAS-II）中最晚被发现的两对复合物，也是一线药物异烟肼靶点InhA的下游蛋白。迄今为止，其三维结构和催化机制尚不清楚。本研究项目可以填补这方面的空白，从分子水平上推进其酶活机制的研究；而HadABC与黄酮类抑制剂和抗结核药物Isoxyl、Thiacetazone复合物结构研究将揭示其抗结核的抑制机制，对基于HadABC的抗结核药物开发提供重要线索和可靠的结构生物学基础。", "英文摘要": "Tuberculosis (TB) is the most lethal and widely spread bacterial infectious disease over the world, mainly caused by the pathogenic Mycobacterium tuberculosis (Mtb). Seriously, the emergence of Multi-drug resistant TB (MDR-TB) and extensively drug resistant TB (XDR-TB) make currently used drugs ineffective to cure TB. Therefore, developing novel and effective anti-TB drugs following research of newly found drug targets has already been an urgent and important mission now. Mtb is hard to kill under host immune attack and survives from toxicant invasion because of the dense and hydrophobic mycolic acid layer of cell wall. Both of HadAB and HadBC were the dehydratases, which were the last and latest identified piece of the type II fatty acid synthesis (FAS-II) system, involved in the elongation of mycolic acid chain. The importance of mycolic acid for Mtb makes all the enzymes in this synthesis pathway potential drug targets including HadAB and HadBC. In fact, they were exact downstream enzymes of InhA, an approved target of currently first-line drug isoniazid. So far as we know, there are no crystal structures of HadAB and HadBC reported and the knowledge of catalytic mechanism is unclear as well. Thus, our research will fill in these gaps by deepening our understanding of it enzymatic catalysis from molecular perspective. Our research also aims to unveil inhibition mechanisms by studying the complex structures of HadABC with either flavonoid inhibitors or anti-TB drugs Isoxyl and Thiacetazone, which will lay sound structural basis and provide important clues for the anti-TB drug development.", "负责人职称": "副研究员"}
-{"h": "", "项目名称": "单颗粒低温透射电镜高分辨率数据收集用支持膜的研究", "批准号": "31500608", "项目类别": "青年科学基金项目", "依托单位": "中国科学院生物物理研究所", "项目负责人": "黄小俊", "资助经费(万元)": "20", "批准年度": "2015", "关键词": "冷冻电镜成像技术；单颗粒三维重构；单颗粒冷冻电镜法", "是否结题": "是", "研究成果(期刊论文;会议论文;著作;奖励;专利)": "0;0;0;0;2", "依托单位ID": "100067", "项目负责人ID": "100172851", "项目类别代码": "630", "申请代码": "C050101", "起止年月": "2016-01至2018-12", "中文摘要": "单颗粒低温透射电镜技术发展至今，最大的瓶颈在于样品制备。而样品制备不可或缺的耗材是透射电镜载网。透射电镜载网（特别是覆在其上的支持膜）的亲水性能，机械性能，导电性能等直接影响着制备样品的质量及数据收集效率。本项目在已自主研制并应用的GIG微阵列碳支持膜的基础上，继续研发更符合实际需要的特定厚度、孔径及孔间距的微阵列支持膜，并以提升支持膜的导电性为目标以开发出第二代的该系列微阵列支持膜。最终将第二代的微阵列支持膜应用到低温透射电镜技术中，降低电子束引发的图像漂移状况，提升单颗粒低温透射电镜成像质量和数据收集效率。", "英文摘要": "Single particle cryo electron microscopy develops very fast these years. The bottle neck of this technique is at sample preparation. Among all those important factors of sample preparation, e.g. protein purity, concentration, rigidity et al., the properties of TEM grid, to be specific, the properties of supporting film on the TEM grid, is essential to preparing a good cryo sample. Hydrophilicity, strong mechanical strength, high conductivity of the supporting film affect the quality of prepared cryo sample and the efficiency of data collection. Based on the self-developed amorphous carbon film with fixed-pattern micro array (brand name GIG), this study aims to develop more suitable supporting films for cryoTEM usage. It includes designing suitable film thickness, hole size, spacing between hole which leads to high efficiency data collection, and increasing the conductivity of the supporting film at liquid nitrogen temperature which reduces the beam induce movement and enhances the quality of cryoEM images.", "负责人职称": "高级工程师"}
-{"h": "", "项目名称": "干扰素诱导蛋白IFIT/ISG56家族抗病毒功能的结构生物学研究", "批准号": "31500609", "项目类别": "青年科学基金项目", "依托单位": "中国科学院生物物理研究所", "项目负责人": "冯峰", "资助经费(万元)": "20", "批准年度": "2015", "关键词": "IFIT/ISG56家族蛋白；抗病毒；天然免疫", "是否结题": "是", "研究成果(期刊论文;会议论文;著作;奖励;专利)": "1;0;0;0;0", "依托单位ID": "100067", "项目负责人ID": "100218232", "项目类别代码": "630", "申请代码": "C050101", "起止年月": "2016-01至2018-12", "中文摘要": "病原体和干扰素能够诱导ISG56/IFIT 家族蛋白的表达, 它们不仅具有抗病毒作用，而且还参与调节细胞的免疫反应。前期我们在国际上率先解析了该家族成员的晶体结构，并且通过结构信息证实了其抗病毒功能与核酸结合能力有关，但是其背后的分子机制尚不明确。本项目拟通过结构生物学结合细胞生物学的手段，在已获得的研究结果基础上系统地开展ISG56/IFIT 家族各个成员的抗病毒和免疫功能的分子机制的研究，包括比较家族成员之间的晶体结构差异；明确识别和结合核酸的序列和结构的特异性；检测在免疫反应信号通路中相互作用的分子，最终揭示家族各成员选择性激活表达的条件和特异性抗病毒的原因。本项目的研究成果将对宿主抗病毒天然免疫领域的研究以及相应的免疫临床治疗具有重要的理论和现实意义。", "英文摘要": "ISG56/IFIT family proteins，which be induced by interferon and pathogen，have antiviral functions and can regulate cellular immune response. Previously, we first solved the crystal structure of ISG56/IFIT family proteins and discovered that their antiviral functions are related to their ability to recognize nucleotides. However, the molecular mechanism remains unknown. In this project, we aim to reveal the mechanism of ISG56/IFIT proteins using structural and cellular biology methods. Base on the information on crystal structure differences, nucleic acid recognitions, binding partners in innate immune pathway, we try to propose the mechanism of specificity of ISG56/IFIT family proteins' antiviral functions. Our results will deepen people's understanding on innate immune response and provide practical significance on clinical treatment.", "负责人职称": "博士后"}
-{"h": "", "项目名称": "Wnt信号通路中β-catenin及其细胞核内共激活因子复合物的结构生物学研究", "批准号": "31500610", "项目类别": "青年科学基金项目", "依托单位": "中国科学院生物物理研究所", "项目负责人": "孙伟", "资助经费(万元)": "20", "批准年度": "2015", "关键词": "蛋白质；相互作用；晶体筛选；结构解析；分子置换", "是否结题": "是", "研究成果(期刊论文;会议论文;著作;奖励;专利)": "1;0;0;0;0", "依托单位ID": "100067", "项目负责人ID": "100045287", "项目类别代码": "630", "申请代码": "C050101", "起止年月": "2016-01至2018-12", "中文摘要": "Wnt/β-catenin信号通路的过度激活会导致许多癌症的发生。β-catenin是该通路上的中心效应分子，它的表达上调是这些癌症发生的驱动因素。在细胞核内，多种共激活因子与β-catenin相互作用，共同激活下游肿瘤促进因子如cyclin-D和c-Myc的转录，其中M1型叉头框蛋白（FoxM1）和PCNA相关因子（PAF）就是其中两个。FoxM1促进β-catenin在细胞核内的定位，并可以促进Wnt应激基因的表达，在人类的多种肿瘤（比如神经胶质瘤）中都有过表达。PAF则在结直肠癌和肠干细胞中特异表达。因为β-catenin-FoxM1和β-catenin-PAF复合体的形成是Wnt/β-catenin下游的重要事件，对肿瘤的发生及恶化起重要作用，我们计划对它们开展结构生物学研究，以便阐释相关癌症的发生机理，并为人类癌症治疗提供新的思路。", "英文摘要": "Hyperactivation of the canonical Wnt/β-catenin signaling pathway can cause many types of cancers. β-catenin is the central effector of this signaling pathway, and its upregulation is a driving factor for these cancers. In the nucleus, many coactivators interact with β-catenin, activating transcription of downstream tumor-promoting factors such as cyclin-D and c-Myc. Forhead box protein M1 type (FoxM1) and PCNA-associated factor (PAF) are two β-catenin-specific transcriptional coactivators. FoxM1 promotes β-catenin nuclear localization and induces expression of Wnt responsive genes, and is overexpressed in many cancer types, including glioma. As to PAF, it is specifically expressed in colon cancer and intestine stem cells.  Because formations of β-catenin-FoxM1 and β-catenin-PAF complex are critical events downstream of Wnt/β-catenin signaling pathway, which play vital roles in tumorigenesis and metastasis of many cancers, we embark on investigating the interactions between β-catenin and FoxM1/PAF employing structural biological methods.  We aim to elucidate the molecular mechanism of tumorigenicity and try to provide novel insights into the therapy of human cancers.", "负责人职称": "博士后"}
-{"h": "", "项目名称": "应用电子顺磁共振技术探究结核分枝杆菌分泌系统内膜蛋白Rv3882c跨膜结构域的结构特征", "批准号": "31500611", "项目类别": "青年科学基金项目", "依托单位": "中国科学院合肥物质科学研究院", "项目负责人": "于璐", "资助经费(万元)": "20", "批准年度": "2015", "关键词": "分枝杆菌分泌系统；膜蛋白；位点特异性自旋标记；电子顺磁共振；结构测定", "是否结题": "是", "研究成果(期刊论文;会议论文;著作;奖励;专利)": "2;0;0;0;0", "依托单位ID": "100212", "项目负责人ID": "100134186", "项目类别代码": "630", "申请代码": "C050101", "起止年月": "2016-01至2018-12", "中文摘要": "结核分枝杆菌的ESX-1分泌系统能使菌体分泌的致病因子、存活因子等蛋白质穿过其高度疏水致密的细胞被膜，对结核分枝杆菌的毒力和存活极为关键。因此，有关ESX-1分泌系统相关组成蛋白的结构分析对于理解结核杆菌感染机制具有非常重要的意义。Rv3882c蛋白是ESX-1分泌系统中一种重要的内膜蛋白，可能与其他组成蛋白共同形成通道类复合物，负责转运底物穿过细胞被膜，但目前其空间结构和确切的生物学功能尚不明确，仍亟待研究。本项目将结合位点特异性自旋标记与电子顺磁共振技术，通过获取Rv3882c蛋白跨膜结构域的运动性信息、易趋性信息以及在膜环境中的取向信息，综合分析得到Rv3882c蛋白跨膜结构域在膜环境中的三维结构模型。本项目的顺利开展，将为Rv3882c蛋白的结构研究提供重要依据，有助于进一步阐明结核分枝杆菌的分泌系统与致病机制，也为应用电子顺磁共振技术研究其他膜蛋白结构提供方法与思路。", "英文摘要": "The ESX-1 secretion system of Mycobacterium tuberculosis serves to secrete proteins, such as virulence factors and survival factors, across its highly hydrophobic and poorly permeable cell envelop, which is crucial for the virulence and survival of Mycobacterium tuberculosis. Therefore, structural investigation on component proteins of ESX-1 secretion system is very important for understanding the infection mechanisms of Mycobacterium tuberculosis. Rv0082c is a very important membrane protein of ESX-1 secretion system and is located on the inner membrane of Mycobacterium tuberculosis. It was predicted that Rv3382c forms a channel-like complex with other proteins and functions to transport the substrates across the mycobacterial cell envelope. However, the structure and function of this protein is still unclear. In this proposal, we are trying to characterize the structure of the transmembrane domain of membrane protein Rv3882c by combing Site Directed Spin Labelling (SDSL) technology and Electron Paramagnetic Resonance (EPR) spectroscopy. The acquired mobility, accessibility and orientation information in membrane will be integrated to derive a three dimensional structural model of the transmembrane domain of Rv3882c. Successful implementation of this project will not only yield valuable information for structural determination of Rv3882c, but also provide deeper insights of the protein secretion system and pathogenic mechanism of Mycobacterium tuberculosis. Also, this project will provide method of using EPR as the tool for structural studies of other membrane proteins.", "负责人职称": "副研究员"}
-{"h": "", "项目名称": "真核生物mRNA转录出核复合物TREX-1的结构与功能研究", "批准号": "31500612", "项目类别": "青年科学基金项目", "依托单位": "许昌学院", "项目负责人": "苏测洋", "资助经费(万元)": "20", "批准年度": "2015", "关键词": "mRNA转录出核复合物；THO复合物；蛋白质结构生物学；X-射线晶体学；冷冻电镜", "是否结题": "是", "研究成果(期刊论文;会议论文;著作;奖励;专利)": "0;0;0;0;0", "依托单位ID": "400411", "项目负责人ID": "100181698", "项目类别代码": "630", "申请代码": "C050101", "起止年月": "2016-01至2018-12", "中文摘要": "真核生物mRNA转录出核复合物TREX-1广泛存在于从酵母到哺乳动物中，参与mRNA的转录、转录后加工和出核运输等一系列过程。有报道指出，TREX-1复合物组分在很多癌症组织中检测到表达异常。TREX-1复合物在真核生物中保守性较高，酵母源TREX-1复合物由Sub2、Yra1和THO复合物组成，人源TREX-1复合物由Uap56、Yra1以及人源THO复合物组成。目前，缺乏TREX-1复合物的高分辨率三维结构，这极大的阻碍了对其参与pre-mRNA加工分子机理的深入研究。我们之前的研究通过昆虫杆状病毒体外重组表达获得了高纯度的酵母源THO复合物。在此基础上，本项目拟对酵母和人源的TREX-1复合物进行组装与纯化，通过结合蛋白质X射线晶体学和冷冻电镜技术，以期获得TREX-1复合物高分辨率三维结构，并辅以生物化学和细胞生物学技术，研究其组装及参与mRNA出核的分子机制。", "英文摘要": "Eukaryotic mRNA TRanscription/EXport complex-1 (TREX-1 complex) is evolutionarily conserved multi-protein complex from yeast to human, participating in mRNA transcription, post-transcription processing and export. Previous report indicated that different protein component of TREX-1 complex has dysregulated expressed in different cancer specimens. Yeast TREX-1 complex consists Sub2, Yra1 and THO complex, while human TREX-1 complex consists Uap56 (yeast Sub2 homologous protein), Aly (yeast Yra1 homologous protein) and human THO complex. The detail mechanism of how TREX-1 complex participate pre-mRNA maturation and export is still obscurity, due to the miss of high-resolution 3D structural model of TREX-1 complex. In previous study, we get highly purified yeast THO complex through recombinant baculovirus expression system. Based on these, we try to reconstitute yeast and human TREX-1 complex in vivo and in vitro, through protein X-ray crystallography and cyro-EM technology, aim to get high-resolution 3D structure of TREX-1 complex. We also try to use biochemical and cell biology method to investigate the molecular mechanism of TREX-1 assembling and its participation mRNA export.", "负责人职称": "讲师"}
-{"h": "", "项目名称": "一种新的葡萄糖脱氢酶FAD-GDH的晶体结构与催化机制研究", "批准号": "31560244", "项目类别": "地区科学基金项目", "依托单位": "遵义医科大学", "项目负责人": "杨愈丰", "资助经费(万元)": "40", "批准年度": "2015", "关键词": "", "是否结题": "否", "研究成果(期刊论文;会议论文;著作;奖励;专利)": "0;0;0;0;0", "依托单位ID": "", "项目负责人ID": "", "项目类别代码": "631", "申请代码": "C050101", "起止年月": "2016-01至2019-12", "中文摘要": "", "英文摘要": "", "负责人职称": ""}
-{"h": "", "项目名称": "高等植物PSII-LHCII超复合物的三维结构研究", "批准号": "31570724", "项目类别": "面上项目", "依托单位": "中国科学院生物物理研究所", "项目负责人": "曹鹏", "资助经费(万元)": "70", "批准年度": "2015", "关键词": "", "是否结题": "否", "研究成果(期刊论文;会议论文;著作;奖励;专利)": "0;0;0;0;0", "依托单位ID": "", "项目负责人ID": "", "项目类别代码": "218", "申请代码": "C050101", "起止年月": "2016-01至2019-12", "中文摘要": "", "英文摘要": "", "负责人职称": ""}
-{"h": "", "项目名称": "铁吸收调控蛋白Fur的复合物结构和识别机制研究", "批准号": "31570725", "项目类别": "面上项目", "依托单位": "中国农业大学", "项目负责人": "陈忠周", "资助经费(万元)": "65", "批准年度": "2015", "关键词": "", "是否结题": "否", "研究成果(期刊论文;会议论文;著作;奖励;专利)": "0;0;0;0;0", "依托单位ID": "", "项目负责人ID": "", "项目类别代码": "218", "申请代码": "C050101", "起止年月": "2016-01至2019-12", "中文摘要": "", "英文摘要": "", "负责人职称": ""}
-{"h": "", "项目名称": "中介体核心复合物调控RNA聚合酶II的结构机制研究", "批准号": "31570726", "项目类别": "面上项目", "依托单位": "中国科学技术大学", "项目负责人": "王雪娟", "资助经费(万元)": "60", "批准年度": "2015", "关键词": "", "是否结题": "否", "研究成果(期刊论文;会议论文;著作;奖励;专利)": "0;0;0;0;0", "依托单位ID": "", "项目负责人ID": "", "项目类别代码": "218", "申请代码": "C050101", "起止年月": "2016-01至2019-12", "中文摘要": "", "英文摘要": "", "负责人职称": ""}
-{"h": "", "项目名称": "基于冷冻电镜的呼肠孤病毒转录的分子机制研究", "批准号": "31570727", "项目类别": "面上项目", "依托单位": "清华大学", "项目负责人": "程凌鹏", "资助经费(万元)": "62", "批准年度": "2015", "关键词": "", "是否结题": "否", "研究成果(期刊论文;会议论文;著作;奖励;专利)": "0;0;0;0;0", "依托单位ID": "", "项目负责人ID": "", "项目类别代码": "218", "申请代码": "C050101", "起止年月": "2016-01至2019-12", "中文摘要": "", "英文摘要": "", "负责人职称": ""}
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-{"h": "", "项目名称": "分泌系统内新型激酶的结构和底物识别机制研究", "批准号": "31570735", "项目类别": "面上项目", "依托单位": "北京大学", "项目负责人": "肖俊宇", "资助经费(万元)": "62", "批准年度": "2015", "关键词": "", "是否结题": "否", "研究成果(期刊论文;会议论文;著作;奖励;专利)": "0;0;0;0;0", "依托单位ID": "", "项目负责人ID": "", "项目类别代码": "218", "申请代码": "C050101", "起止年月": "2016-01至2019-12", "中文摘要": "", "英文摘要": "", "负责人职称": ""}
-{"h": "", "项目名称": "衣原体III型分泌系统结构的低温电镜研究", "批准号": "31570736", "项目类别": "面上项目", "依托单位": "中山大学", "项目负责人": "张勤奋", "资助经费(万元)": "60", "批准年度": "2015", "关键词": "", "是否结题": "否", "研究成果(期刊论文;会议论文;著作;奖励;专利)": "0;0;0;0;0", "依托单位ID": "", "项目负责人ID": "", "项目类别代码": "218", "申请代码": "C050101", "起止年月": "2016-01至2019-12", "中文摘要": "", "英文摘要": "", "负责人职称": ""}
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-{"h": "", "项目名称": "光合玫瑰菌核心光合复合体的结构与功能研究", "批准号": "31570738", "项目类别": "面上项目", "依托单位": "杭州师范大学", "项目负责人": "徐晓玲", "资助经费(万元)": "62", "批准年度": "2015", "关键词": "", "是否结题": "否", "研究成果(期刊论文;会议论文;著作;奖励;专利)": "0;0;0;0;0", "依托单位ID": "", "项目负责人ID": "", "项目类别代码": "218", "申请代码": "C050101", "起止年月": "2016-01至2019-12", "中文摘要": "", "英文摘要": "", "负责人职称": ""}
-{"h": "", "项目名称": "神经肽Y受体NPY1R的结构生物学研究", "批准号": "31570739", "项目类别": "面上项目", "依托单位": "中国科学院上海药物研究所", "项目负责人": "吴蓓丽", "资助经费(万元)": "70", "批准年度": "2015", "关键词": "", "是否结题": "否", "研究成果(期刊论文;会议论文;著作;奖励;专利)": "0;0;0;0;0", "依托单位ID": "", "项目负责人ID": "", "项目类别代码": "218", "申请代码": "C050101", "起止年月": "2016-01至2019-12", "中文摘要": "", "英文摘要": "", "负责人职称": ""}
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-{"h": "", "项目名称": "Liprin-α介导的神经突触形成中活性区组装机制的研究", "批准号": "31570741", "项目类别": "面上项目", "依托单位": "南方科技大学", "项目负责人": "魏志毅", "资助经费(万元)": "62", "批准年度": "2015", "关键词": "", "是否结题": "否", "研究成果(期刊论文;会议论文;著作;奖励;专利)": "0;0;0;0;0", "依托单位ID": "", "项目负责人ID": "", "项目类别代码": "218", "申请代码": "C050101", "起止年月": "2016-01至2019-12", "中文摘要": "", "英文摘要": "", "负责人职称": ""}
-{"h": "", "项目名称": "基于冷冻电镜二十面体对称失配三维重构的腺病毒结构研究", "批准号": "31570742", "项目类别": "面上项目", "依托单位": "湖南师范大学", "项目负责人": "刘红荣", "资助经费(万元)": "62", "批准年度": "2015", "关键词": "", "是否结题": "否", "研究成果(期刊论文;会议论文;著作;奖励;专利)": "0;0;0;0;0", "依托单位ID": "", "项目负责人ID": "", "项目类别代码": "218", "申请代码": "C050101", "起止年月": "2016-01至2019-12", "中文摘要": "", "英文摘要": "", "负责人职称": ""}
-{"h": "", "项目名称": "糖原代谢关键蛋白质的结构和功能研究", "批准号": "31570743", "项目类别": "面上项目", "依托单位": "中国科学院上海生命科学研究院", "项目负责人": "向嵩", "资助经费(万元)": "60", "批准年度": "2015", "关键词": "", "是否结题": "否", "研究成果(期刊论文;会议论文;著作;奖励;专利)": "0;0;0;0;0", "依托单位ID": "", "项目负责人ID": "", "项目类别代码": "218", "申请代码": "C050101", "起止年月": "2016-01至2019-12", "中文摘要": "", "英文摘要": "", "负责人职称": ""}
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-{"h": "", "项目名称": "内吞性胶原蛋白受体Endo180 的结构研究", "批准号": "31570745", "项目类别": "面上项目", "依托单位": "福州大学", "项目负责人": "袁彩", "资助经费(万元)": "62", "批准年度": "2015", "关键词": "", "是否结题": "否", "研究成果(期刊论文;会议论文;著作;奖励;专利)": "0;0;0;0;0", "依托单位ID": "", "项目负责人ID": "", "项目类别代码": "218", "申请代码": "C050101", "起止年月": "2016-01至2019-12", "中文摘要": "", "英文摘要": "", "负责人职称": ""}
-{"h": "", "项目名称": "线粒体解偶联蛋白UCP1的结构和功能解析", "批准号": "31570746", "项目类别": "面上项目", "依托单位": "中国科学院上海生命科学研究院", "项目负责人": "周界文", "资助经费(万元)": "65", "批准年度": "2015", "关键词": "", "是否结题": "否", "研究成果(期刊论文;会议论文;著作;奖励;专利)": "0;0;0;0;0", "依托单位ID": "", "项目负责人ID": "", "项目类别代码": "218", "申请代码": "C050101", "起止年月": "2016-01至2019-12", "中文摘要": "", "英文摘要": "", "负责人职称": ""}
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-{"h": "", "项目名称": "负链RNA病毒聚合酶的结构和功能机制研究", "批准号": "31530015", "项目类别": "重点项目", "依托单位": "中国科学院生物物理研究所", "项目负责人": "刘迎芳", "资助经费(万元)": "292", "批准年度": "2015", "关键词": "", "是否结题": "否", "研究成果(期刊论文;会议论文;著作;奖励;专利)": "0;0;0;0;0", "依托单位ID": "", "项目负责人ID": "", "项目类别代码": "220", "申请代码": "C050101", "起止年月": "2016-01至2020-12", "中文摘要": "", "英文摘要": "", "负责人职称": ""}
-{"h": "", "项目名称": "染色体的结构与功能研究", "批准号": "31525007", "项目类别": "国家杰出青年科学基金", "依托单位": "上海交通大学", "项目负责人": "雷鸣", "资助经费(万元)": "350", "批准年度": "2015", "关键词": "", "是否结题": "否", "研究成果(期刊论文;会议论文;著作;奖励;专利)": "0;0;0;0;0", "依托单位ID": "", "项目负责人ID": "", "项目类别代码": "429", "申请代码": "C050101", "起止年月": "2016-01至2020-12", "中文摘要": "", "英文摘要": "", "负责人职称": ""}
+{"项目名称": "脱敏态GluA2配体结合域LBD二聚体系综结构及其调控的研究", "批准号": "31500595", "项目类别": "青年科学基金项目", "依托单位": "浙江大学", "项目负责人": "刘主", "资助经费(万元)": "20", "批准年度": "2015", "关键词": "谷氨酸受体；脱敏；顺磁核磁共振；小角X光散射；蛋白质系综结构", "是否结题": "是", "研究成果(期刊论文;会议论文;著作;奖励;专利)": "2;0;0;0;0", "依托单位ID": "100152", "项目负责人ID": "100145756", "项目类别代码": "630", "申请代码": "C050101", "起止年月": "2016-01至2018-12", "中文摘要": "研究蛋白质系综结构及分布比例使我们了解蛋白质如何行使功能。离子型谷氨酸受体2（GluA2）参与脑内重要的生理和病理过程。研究表明，GluA2为二聚—二聚组成的四聚体，其配体结合域（LBD）二聚体结构的变化对GluA2的配体门控至关重要。由于GluA2的LBD二聚作用极弱（KD值约为6mM），因此对其结构研究极少。最近我们实验发现，在脱敏条件下，LBD的瞬态二聚体存在多种构象。为解析脱敏态LBD二聚体原子分辨率的系综结构及分布比例，本项目拟采用化学交联质谱分析的方法获得低分辨率的系综构象和分布，同时运用顺磁弛豫增强的液体核磁共振技术解析原子分辨的系综结构，并联合小角X光散射以计算各构象比例。基于LBD二聚体的结构，我们将突变界面关键位点，结合电生理，阐明全长GluA2脱敏过程与脱敏态LBD二聚体系综结构的构效关系。据此，我们将从脱敏态LBD二聚体结构动态变化的角度揭示GluA2的脱敏机制。", "英文摘要": "Depiction of protein ensemble structure has allowed us to understand how the protein fulfills its function. Ionic glutamate acceptor 2 (GluA2) is involved in many important physiological and pathological processes in the brain. GluA2 is tetrameric (dimer of dimer), and its ligand binding domain (LBD) dimer plays a key role in the ligand gating of GluA2. As the LBD only weakly dimerizes by itself, there has been few studies on the ensemble structure of LBD dimer. We found that the LBD dimer adopts an array of relative orientations as the GluA2 shifts into the desensitized state. We thus propose to determine the ensemble structure of LBD dimer. We will use the CXMS (chemical cross-linking of proteins coupled with mass spectrometry analysis) analysis to obtain a low-resolution picture. Conjointly, we will use PRE (paramagnetic relaxation enhancement) NMR to further characterize the ensemble structure of LBD dimer, and use SAXS (small-angle x-ray scattering) to assess the relative populations of each conformational state. Based on the structural characterization, we will mutate key interfacial residues that may perturb the ensemble structure of LBD dimer, which will be confirmed by electrophysiological analyses. Together, we will illustrate how the structural change of LBD dimer accompanies the desensitization of GluA2. If funded and successfully carried out, the project will provide the structural basis for exquisite pharmacological modulation of GluA2 function.", "负责人职称": "教授"}
+{"项目名称": "帕金森病致病蛋白LRRK2的ROC结构域GTP水解抑制机制与结构生物学研究", "批准号": "31500596", "项目类别": "青年科学基金项目", "依托单位": "南京理工大学", "项目负责人": "廖静伶", "资助经费(万元)": "20", "批准年度": "2015", "关键词": "富亮氨酸重复激酶2；ROC结构域；GTP水解活性；结构功能学；帕金森病", "是否结题": "是", "研究成果(期刊论文;会议论文;著作;奖励;专利)": "2;0;0;0;0", "依托单位ID": "100468", "项目负责人ID": "100118874", "项目类别代码": "630", "申请代码": "C050101", "起止年月": "2016-01至2018-12", "中文摘要": "帕金森病是与年龄密切相关的神经退行性疾病之一。LRRK2基因是目前为止突变率最高的帕金森病致病基因，主要表现在LRRK2蛋白激酶活性的异常增高，但其具体生物功能及致病机制仍不明确。深入研究LRRK2蛋白正常生理功能及基因突变的致病机制将为研究帕金森病治疗策略提供分子机制水平的依据。LRRK2蛋白除了具有激酶活性以外，还拥有GTP水解酶活性，该GTP水解酶活性对激酶活性有调节作用，揭示LRRK2蛋白存在分子内调节机制。LRRK2蛋白特有的生化特征使其成为帕金森病非常有希望的治疗靶点。申请者将运用X射线蛋白晶体学，生物化学及生物物理学方法，通过解析LRRK2蛋白中的ROC结构域晶体结构及GTP水解抑制机制来阐明基因突变的致病机理，为新的通过调控GTP水解酶活性来降低LRRK2的激酶活性的方法提供理论依据。", "英文摘要": "Parkinson’s disease (PD) is a devastating neurological condition that ravages people’s quality of life as it progresses from the subtle loss of muscular coordination, to severe physical and mental disability, to eventual death. There is no cure and no available treatments to stop this disease progression. Today, mutations in LRRK2 are the most prevalent known genetic causes of Parkinson’s disease, for both familial and sporadic cases. In spite of the intensive efforts over the past decade, the molecular role of LRRK2 in disease pathogenesis, its function, and the effects of disease-causing mutations remain unknown. Understanding the underlying mechanism of LRRK2 normal function and how it is affected by the disease-associated mutations will reveal novel mechanism-based therapeutic strategies. In addition to LRRK2 being associated with PD and being the most promising drug target for the disease, LRRK2 is an immensely intriguing protein, in that it has two enzymatic activities (GTPase activity and Kinase activity) that, together with other non-enzymatic domains, potentially represent a unique example of an intramolecular signaling system. The concept of the Roc GTPase domain functioning as a molecular switch regulating the overall activity of LRRK2 is conceptually interesting from a biochemical perspective, and it is the key to LRRK2’s normal function and disease process. In addition to the relatively wide prevalence of LRRK2 in PD, it is the most attractive target for drug discovery, because over-activation of its kinase activity is linked to disease pathogenesis, and it is an enzyme with active sites well suited for binding potential drugs. Indeed, LRRK2 kinase activity was effectively inhibited by broad kinase inhibitors that compete for ATP in the ATP-binding pocket. However, their translation into the clinic has been difficult due to adverse effects. Various potential alternative strategies are being considered, including targeting the Roc domain. This proposed study seeks to define the structures of ROC domain and its mutants to understand the GTP hydrolysis mechanism and mutations pathogenesis by using X-ray diffraction crystallography, protein biochemistry and biophysics approaches, which could provide insight into locations on LRRK2 structures that are suitable for mechanism-based drug discovery.", "负责人职称": "副教授"}
+{"项目名称": "线性泛素链组装复合物(LUBAC)的调节机制研究", "批准号": "31500597", "项目类别": "青年科学基金项目", "依托单位": "中国科学院上海有机化学研究所", "项目负责人": "刘建平", "资助经费(万元)": "20", "批准年度": "2015", "关键词": "蛋白质复合物；X射线晶体衍射；泛素化；肿瘤坏死因子TNFα；细胞死亡", "是否结题": "是", "研究成果(期刊论文;会议论文;著作;奖励;专利)": "4;0;0;0;0", "依托单位ID": "400014", "项目负责人ID": "100193226", "项目类别代码": "630", "申请代码": "C050101", "起止年月": "2016-01至2018-12", "中文摘要": "线性泛素化是一类广泛参与炎症和先天免疫的新型泛素化修饰。迄今唯一的线性泛素链E3连接酶LUBAC复合物由调节亚基Sharpin、HOIL1和催化亚基HOIP组成。单独的HOIP处于自抑制状态，但可以被Sharpin或HOIL1激活。然而，HOIP的自抑制和激活、与Sharpin的相互作用机制仍然未知。Sharpin缺失小鼠表现出多器官炎症和TNFα通路异常。为了阐明LUBAC复合物的调控机制，本申请计划解析自抑制和激活状态的HOIP催化核心片段，以及Sharpin/HOIP复合物的结构，揭示HOIP的自抑制和激活机制，并设计点突变解除自抑制或者破坏Sharpin对HOIP的激活，研究相应突变体对细胞死亡或RIP1线性泛素化的影响，以检验我们的假说：Sharpin/HOIP复合物对RIP1的线性泛素化决定了TNFα通路的最终效应——炎症或细胞死亡。现有工作进展为实现上述目标奠定了坚实的基础。", "英文摘要": "Linear ubiquitination, a recently discovered novel type of ubiquitination, is extensively involved in numerous signaling pathways related to inflammation and innate immune. Linear ubiquitin chain assembly complex (LUBAC) is the sole identified E3 ubiquitin ligase that catalyzes the formation of linear poly-ubiquitin chain. It consists of two regulatory subunits Sharpin and HOIL1 as well as one catalytic subunit HOIP. The isolated HOIP is in an auto-inhibited state, but it can be activated by Sharpin or HOIL1 to sufficiently promote the linear ubiquitination of target substrates. However, the molecular mechanisms underlying the the auto-inhibition of HOIP, its activation by Sharpin or HOIL1, and the interaction between HOIP and Sharpin are largely unknown. Previous studies indicated that loss of Sharpin in the mouse caused immunodeficiency and multi-organ inflammation, and severely inhibited the linear ubiquitination of TNFα receptor signaling complex. Based on these findings, we propose a hypothesis: the linear ubiquitination level of RIP1 catalyzed by Sharpin/HOIP complex determines the outcome of TNFα signaling—inflammation or cell death. To further understand the regulatory mechanism of LUBAC complex, we aimed to solve the structures of the catalytic fragment of HOIP either in auto-inhibited or in activated states as well as the Sharpin/HOIP complex, thereby to uncover the auto-inhibition and activation mechanism of HOIP. Based on the solved structures, we will design point mutations to specifically disrupt the auto-inhibition or the trans-activation of HOIP mediated by Sharpin; we will further test our hypothesis by assessing the impact of these mutations on the linear ubiquitination level of RIP1 and the TNFα induced cell death. Our current research progress has laid the foundation for us to pursue the scientific goals in this proposal.", "负责人职称": "副研究员"}
+{"项目名称": "转录因子CcmR调控蓝细菌碳浓缩机制的结构生物学基础", "批准号": "31500598", "项目类别": "青年科学基金项目", "依托单位": "中国科学技术大学", "项目负责人": "成望", "资助经费(万元)": "20", "批准年度": "2015", "关键词": "蓝藻；碳浓缩机制；转录调控；晶体结构；异构效应", "是否结题": "是", "研究成果(期刊论文;会议论文;著作;奖励;专利)": "1;0;0;0;0", "依托单位ID": "200654", "项目负责人ID": "100047316", "项目类别代码": "630", "申请代码": "C050101", "起止年月": "2016-01至2018-12", "中文摘要": "蓝细菌是被广泛用于光合作用和碳浓缩机制(CO2-concentrating mechanism, CCM)研究的重要模式生物。CcmR是集胞藻PCC6803中的一个调控碳浓缩机制的全局性转录因子，在低碳信号下解除对CCM相关基因的抑制，引起表达上调，促进CO2的吸收，保证光合作用的顺利进行。我们将以CcmR apo-form四聚体晶体结构为基础，综合利用生物信息学、生物化学、分子生物学以及结构生物学手段，对CcmR与DNA和/或信号分子的相互作用及其二元和三元晶体结构进行系统研究，以期揭示CcmR的别构机理，并基于CcmR特异性识别的DNA序列鉴定其调控的下游基因网络。该项目将阐明CcmR的调控碳浓缩机制的结构基础，有望为生态平衡和农业生产提供理论指导。", "英文摘要": "Cyanobacterium is an ideal model for studying the photosynthesis and CO2-concentration mechanism (CCM). The transcriptional factor CcmR was first identified in the cyanobacterium Synechocystis sp. PCC6803. It serves as a global controller to increase the expression of CCM related genes, which are suppressed at a high Ci concentration, thus augmenting the uptake of CO2 for the efficacy photosynthesis. Based on our previously determined crystal structure of the apo-form CcmR tetramer, we will systematically investigate the interactions of CcmR with the putative allosteric molecule and its binding DNA, by combining the methodologies of bioinformatics, biochemistry, molecular biology and structural biology. The findings will enable us to elucidate the CcmR allosteric mechanism, and to identify the gene network under the control of CcmR. This project will provide insights into the CCM regulated by CcmR, and might be helpful for guiding the ecological balance control and agricultural production in the future.", "负责人职称": "博士后"}
+{"项目名称": "三维超分辨技术研究细胞核孔复合物的选择性屏障分布", "批准号": "31500599", "项目类别": "青年科学基金项目", "依托单位": "复旦大学", "项目负责人": "马炯", "资助经费(万元)": "21", "批准年度": "2015", "关键词": "细胞核孔复合物；FG屏障；单分子；超分辨显微镜；核孔传输", "是否结题": "是", "研究成果(期刊论文;会议论文;著作;奖励;专利)": "9;0;0;0;0", "依托单位ID": "201361", "项目负责人ID": "100162892", "项目类别代码": "630", "申请代码": "C050101", "起止年月": "2016-01至2018-12", "中文摘要": "细胞核孔复合物（NPC）是真核细胞中连接细胞质和细胞核之间的选择性双向通道。由富含苯丙氨酸-甘氨酸（FG）氨基酸片段的自然非折叠蛋白构成的FG-屏障,选择性地调控基因相关物质,按照被动运输或者主动介入运输的方式进出细胞核。然而，核孔内FG屏障间的相互作用以及分布状况仍然是极具争议的重要科学问题。本项目将基于申请人发明的单点斜入射激发快速超分辨显微镜技术，研究核孔传输蛋白或FG-蛋白片段与FG屏障反应的三维分布图像，从而获得FG-屏障在细胞核孔内完整的分布情况。另外,进一步检测核孔传输蛋白对FG屏障的分布影响，讨论核孔传输的自调控机制。还将从不同传输蛋白或FG-片段在传输过程中的竞争效果，讨论FG屏障对各类基因相关物质传输的优先顺序。最终，完整的三维FG屏障将对核孔蛋白缺失相关的白血病、阿尔兹海默症的致病机制，以及各种类病毒的侵入机制等核孔相关病理机制或基因治疗提供信息。", "英文摘要": "The nuclear pore complexes (NPCs) selectively mediate the bidirectional trafficking of macromolecules between the cytoplasm and the nucleus in eukaryotic cells. The selective barrier formed by natively unfolded phenylalanine-glycine (FG) nucleoporins (Nups) inside the NPC allows for passive and facilitated transport through the NPC. However, the interactions that form the FG-barrier and their spatial distribution in the NPC remain unresolved. Based on the single-point edge-excitation sub-diffusion (SPEED) microscopy techniques, the applicant's invention, three-dimensionally map the interaction distributions between the fluorescent transport receptors (TRs) or FG-fragment and FG barrier. Then, we obtain fully information of the FG-barrier distribution in the NPC. The conformation change of the FG-barrier by TRs would be discussed as self-regulating mechanism of nucleocytoplasmic transport. Also from the competitive effects during different FG-fragments and transport proteins during the transport discuss priorities for the various gene related transport. Finally，the complete three-dimensional FG-barrier distribution will provide information with leukemia, Alzheimer's disease pathogenesis, as well as various types of viruses invade mechanisms for NPC related pathological mechanism or gene therapy.", "负责人职称": "研究员"}
+{"项目名称": "成肌细胞融合蛋白myomaker的结构基础与作用机理", "批准号": "31500600", "项目类别": "青年科学基金项目", "依托单位": "清华大学", "项目负责人": "龚德顺", "资助经费(万元)": "9", "批准年度": "2015", "关键词": "膜蛋白；均一性；晶体筛选；结构解析；晶体结构", "是否结题": "是", "研究成果(期刊论文;会议论文;著作;奖励;专利)": "0;0;0;0;0", "依托单位ID": "201260", "项目负责人ID": "100177698", "项目类别代码": "630", "申请代码": "C050101", "起止年月": "2016-01至2016-12", "中文摘要": "Myomaker是新发现的一种可以直接调控成肌细胞融合和肌肉再生的蛋白，这是哺乳动物细胞中唯一一个被鉴定的肌肉特异性的调节蛋白。它促进成肌细胞融合以及肌肉再生的活性为受伤后的肌肉再生提供了新的机会，为肌肉性疾病的治疗提供了新的思路。然而，目前对其发挥功能的分子机理仍然一无所知。本项目拟从结构生物学的角度出发，解析其晶体结构，揭示其分子作用机理。", "英文摘要": "Myomaker, a new discovered myoblast fusion activator, which is the only identified muscle-specific protein that directly regulates myoblast fusion and muscle regeneration in mammals. These activities of myomaker provide new opportunities for muscle regeneration and new strategies for therapy of muscle diseases. However, the molecular mechanism of myomaker is still in the dark. The aim of this project is to determinate the crystal structure of myomaker and provide new insights into the functional mechanism of myomaker.", "负责人职称": "博士后"}
+{"项目名称": "布氏锥虫中参与基因转录调控的PAF1复合物的结构和功能研究", "批准号": "31500601", "项目类别": "青年科学基金项目", "依托单位": "中国科学技术大学", "项目负责人": "廖善晖", "资助经费(万元)": "20", "批准年度": "2015", "关键词": "PAF1复合物；转录调控；布氏锥虫；蛋白质结构；蛋白质相互作用", "是否结题": "是", "研究成果(期刊论文;会议论文;著作;奖励;专利)": "11;0;0;0;1", "依托单位ID": "200654", "项目负责人ID": "100186764", "项目类别代码": "630", "申请代码": "C050101", "起止年月": "2016-01至2018-12", "中文摘要": "真核生物基因转录的调控在时间和空间上都具有很高的复杂度，细胞内基因转录调节的异常与各类疾病密切相关。在研究转录调节的过程中，大量RNA聚合酶相关蛋白复合体被报道，其中PAF1复合物（RNA polymerase II associated factor complex, PAF1C）就是最近发现的一种。PAF1复合物含有至少 5个不同的蛋白亚基，能够协同其他的转录因子及组蛋白修饰酶来调控转录过程。锥虫是一类单细胞真核原生生物，能够引起多种锥虫病。目前在布氏锥虫属中发现的PAF1复合体组成与高等真核生物不完全保守，可能暗示了布氏锥虫特有的基因转录调节方式。本项研究将结合结构生物学和细胞生物学方法，研究布氏锥虫中PAF1复合物的结构及其在基因转录调控中的作用。本研究不仅将丰富我们对布氏锥虫PAF1复合物和基因转录调控的认识，对于我们了解真核生物PAF1复合物和基因转录调控的进化也具有重要意义。", "英文摘要": "Eukaryotic gene transcription regulation is extremely complex in space and time. Any defect of transcription process is closely related to a variety of diseases. Many protein complexes have been reported during the study of transcription regulation, PAF1C (RNA polymerase II associated factor 1 complex) is such a complex discovered recently. PAF1C, contains at least 5 subunits. It participates in gene transcription regulation cooperatively with other transcription factors and histone modification enzymes. Trypanosomatids, the causative pathogens of trypanosomiasis, are a group of unicellular protozoa. The compositions of PAF1C of Trypanosoma brucei (T. brucei) is not fully conserved with that from higher eukaryotes, which may imply species-specific regulation pathway of gene transcription. Here, we are trying to explore the structure of PAF1C and its role in gene transcription regulation in T. brucei, by combining the techniques of structural biology and cell biology. This study will not only enrich our knowledge of PAF1C’s role in transcription regulation in T. brucei, but also has important implications for our understanding of the evolution of eukaryotic PAF1 complex and gene transcription regulation.", "负责人职称": "副研究员"}
+{"项目名称": "铜绿微囊藻气囊蛋白的结构和功能研究", "批准号": "31500602", "项目类别": "青年科学基金项目", "依托单位": "中国科学技术大学", "项目负责人": "代亚男", "资助经费(万元)": "20", "批准年度": "2015", "关键词": "铜绿微囊藻；气囊；气囊蛋白；晶体结构；结构蛋白", "是否结题": "是", "研究成果(期刊论文;会议论文;著作;奖励;专利)": "0;0;0;0;0", "依托单位ID": "200654", "项目负责人ID": "100047317", "项目类别代码": "630", "申请代码": "C050101", "起止年月": "2016-01至2018-12", "中文摘要": "铜绿微囊藻是一种单细胞浮游蓝藻，能大量产生气囊，营养丰富时在淡水水体表面聚集暴发水华。气囊是一种完全由蛋白质组成的中空、充满气体的惰性结构。气囊为藻细胞提供浮力，使其自行调节在自然水体中的垂直位置，漂浮到氧气和光照都适宜的位置以利于自身生长和生境殖民化。气囊不仅是铜绿微囊藻能成为优势藻种的重要原因之一，也在水华的暴发过程中起到了调节作用。然而，人们至今尚未弄清气囊的结构及其合成降解机制。为了探究气囊合成相关蛋白的三维结构，进一步重构气囊这一中空结构的三维面貌，我们以铜绿微囊藻Microcystis aeruginosa PCC 7806中的气囊合成相关的一组Gvp蛋白为研究对象，利用X射线晶体学手段解析各个气囊蛋白的结构，并联合运用高分辨率冷冻电镜，蛋白质免疫印迹法和胶体金标记等方法来分析各结构蛋白的具体定位。该项目将解析气囊原子分辨率水平上的三维结构，对治理水华暴发有一定理论指导意义。", "英文摘要": "Microcystis aeruginosa was investigated and identified as a planktonic unicellular cyanobacterium which is responsible for algal bloom in the freshwater environments. In Microcystis cells, an abundant production of intracellular structures, the gas vesicle, an inert, hollow and gas-filled structure, formed solely from proteins, provides cells with buoyancy and regulates their vertical distribution in natural waters. Cyanobacteria could float taxis toward air-liquid interfaces of water environments, positioning themselves at a depth with optimal light and oxygen supply for better growth, subsequent niche colonization and water-bloom formation. However, the fine structure of gas vesicle and its  biosynthesis/degradation mechanisms are still unclear. To determine three dimensional structures of gas vesicle proteins and remodeling the integral hollow structure, we are committed to solve structures of Gvp proteins from Microcystis aeruginosa PCC 7806 using X-ray crystallography. Moreover, in combination with high-resolution cryo-electron microscopy, we will investigate the localization of individual Gvp proteins by immunoblotting and immunogold labeling-based tomography. These findings will provide insights into structural characteristics of gas vesicle and the rational control of algal bloom.", "负责人职称": "博士后"}
+{"项目名称": "膜环境对膜蛋白DAGK结构与功能的影响", "批准号": "31500603", "项目类别": "青年科学基金项目", "依托单位": "中国科学院武汉物理与数学研究所", "项目负责人": "陈艳可", "资助经费(万元)": "20", "批准年度": "2015", "关键词": "膜蛋白结构；固体核磁共振；天然膜；去垢剂；甘油二脂激酶", "是否结题": "是", "研究成果(期刊论文;会议论文;著作;奖励;专利)": "3;0;0;0;0", "依托单位ID": "201322", "项目负责人ID": "100150871", "项目类别代码": "630", "申请代码": "C050101", "起止年月": "2016-01至2018-12", "中文摘要": "膜蛋白的结构与功能深受所处环境的影响。目前，在PDB数据库中收录的膜蛋白结构90%以上是在膜模拟环境—去垢剂胶束中解析的。然而，在去垢剂的环境中，膜蛋白的真实结构能否被维持是备受结构生物学家关注的问题。大肠杆菌甘油二脂激酶(DAGK)是一个很重要的三跨膜蛋白，其三维结构已经被液体核磁共振和X-Ray晶体衍射的方法在去垢剂胶束或脂质立方相中所解析，然而由于环境的不同，得到的结构差别很大，并且这两种结构都不是在DAGK的天然膜环境中进行解析的。固体核磁共振技术可以在接近膜蛋白天然环境的磷脂双层膜中解析其三维结构，是测定与证实膜蛋白结构的有力工具。本项目拟采用固体核磁共振技术在大肠杆菌磷脂膜的环境下对DAGK的三维结构进行解析，并分析不同环境下DAGK活性区域的结构变化，阐释膜蛋白结构与功能对膜环境的依赖性。", "英文摘要": "The structures of membrane proteins are profoundly influenced by membrane–protein interactions. To date, more than 90% structures of membrane protein in the PDB have been determined in membrane mimetic environments-detergent micelles. However, it is very difficult to obtain membrane mimetic environments that support the native structure and function of a membrane protein. Escherichia coli diacylglycerol kinase (DAGK) is a very important transmembrane protein of which three dimensional structure has been determined in detergent micelles or lipid cubic phase by solution-state NMR or X-Ray crystallography. Due to the different membrane mimetic environments, the two structures differ obviously. Solid-state NMR is a powerful tool for studying structures of membrane proteins in the native-like membrane environments. This project aims to use Solid-state NMR to determin the sturcture of DAGK in Escherichia coli total lipids bilayer. Then, we will expain the influence of membrane environments on membrane protein structure and function by comparation the structures of DAGK active domain in different membrane environments.", "负责人职称": "助理研究员"}
+{"项目名称": "与ALS/FTD相关联的C9orf72六核苷酸重复扩增形成G-四链体的结构研究", "批准号": "31500604", "项目类别": "青年科学基金项目", "依托单位": "香港科技大学深圳研究院", "项目负责人": "周波", "资助经费(万元)": "20", "批准年度": "2015", "关键词": "核磁共振；G-四链体；C9orf72六核苷酸重复扩增；肌萎缩性侧索硬化症；额颞叶痴呆", "是否结题": "是", "研究成果(期刊论文;会议论文;著作;奖励;专利)": "2;0;0;0;0", "依托单位ID": "404024", "项目负责人ID": "100175543", "项目类别代码": "630", "申请代码": "C050101", "起止年月": "2016-01至2018-12", "中文摘要": "肌萎缩性侧索硬化症（ALS）和额颞叶痴呆（FTD）是严重的神经退行性疾病。在家族性或散发性ALS/FTD患者中，位于9号染色体第72个开放阅读框基因（C9orf72）的GGGGCC六核苷酸重复扩增（HRE）是最常见的遗传致病因子。以往研究表明，C9orf72 HRE无论是作为DNA或转录的RNA产物，均可折叠成具有不同结构的G-四链体，并与ALS/FTD的致病机理密切相关。由于缺乏相关G-四链体的高分辨率结构信息，C9orf72 HRE形成G-四链体的分子机理仍不清楚。本研究将利用核磁共振技术首次获取C9orf72 HRE DNA及RNA G-四链体的高分辨率结构，对于在ALS/FTD患者中由于此种结构导致的异常转录产物诱发疾病的分子机理提供极有价值的信息，并且为针对C9orf72 HRE G-四链体设计小分子用以靶向调节ALS/ FTD的发病机制奠定必要的结构学基础。", "英文摘要": "Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are devastating neurological diseases. Abnormal expansion of a hexanucleotide repeat, (GGGGCC)n, is the most common genetic cause of familial and sporadic forms of ALS and FTD. This nucleotide repeat element is located in a non-protein-coding region of the C9orf72 gene. Previous studies suggested that the C9orf72 hexanucleotide repeat expansion (HRE), either as DNA or the transcribed RNA, can fold into G-quadruplexes with distinct structures. It could also form transcriptionally induced RNA-DNA hybrids known as R-loops. These structural polymorphisms lead to C9orf72 HRE-containing abortive transcripts, which may aggregate and form RNA foci in patient cells. Despite the critical connection of C9orf72 HRE G-quadruplexes to the pathogenic mechanism of C9orf72 HRE-linked ALS/FTD, the molecular basis of G-quadruplex formation by C9orf72 HRE remains elusive..In this project, we plan to perform systematic biochemical and structural characterizations for C9orf72 HRE G-quadruplexes. First, we will determine the 3D structure of G-quadruplex formed by the C9orf72 HRE DNA. In our preliminary study, we successfully obtained a homogenous DNA sample, d(GGGGCC)4, which favored a monomeric G-quadruplex fold. We have determined the topology of this G-quadruplex DNA using the nuclear magnetic resonance (NMR) approach. It forms a chair-type G-quadruplex with a four-layer antiparallel G-tetra core and three edgewise loops, which is distinct from known structures of chair-type G-quadruplexes. We will further resolve its detailed structure using NMR techniques. We have also successfully obtained a homogeneous C9orf72 HRE RNA sample with sufficient quality for NMR structure determination. Unlike the monomeric d(GGGGCC)4 DNA, this RNA, r(GGGGCC)GGGG, is an asymmetric dimer. We will perform more NMR studies to obtain its 3D structure. As no structure of the C9orf72 HRE G-quadruplex has ever been solved, the structural information of C9orf72 HRE DNA/RNA G-quadruplexes to be obtained in the current project will provide valuable insights into the molecular mechanism of abortive transcripts formation by C9orf72 HRE and RNA foci appearance in ALS/FTD patients. The outcome of the proposed research will not only provide insight into the molecular mechanism underlying the C9orf72 HRE G-quadruplex formation in the etiology of ALS/FTD, but may also lay the necessary basis for designing small molecules that therapeutically target C9orf72 HRE G-quadruplexes for the modulation of ALS/FTD pathogenesis.", "负责人职称": "副研究员"}
+{"项目名称": "Sema-Plexin信号通路中FARP2的结构与功能研究", "批准号": "31500605", "项目类别": "青年科学基金项目", "依托单位": "华中科技大学", "项目负责人": "贺晓静", "资助经费(万元)": "21", "批准年度": "2015", "关键词": "蛋白质结构；相互作用；轴突导向", "是否结题": "是", "研究成果(期刊论文;会议论文;著作;奖励;专利)": "2;0;0;0;0", "依托单位ID": "100113", "项目负责人ID": "100154722", "项目类别代码": "630", "申请代码": "C050101", "起止年月": "2016-01至2018-12", "中文摘要": "神经系统的精确发育发展离不开轴突导向。神经细胞生长椎上的受体接受环境中的轴突导向因子传递的信号，经过一系列蛋白的传递，最后作用于细胞骨架蛋白，从而影响生长椎的走向。Semaphorin-Plexin 通路是其中重要的信号通路之一，我们的研究重点是这一通路中plexin的下游互作蛋白FARP2。FARP2 N端的FERM结构域介导它与Plexin之间的相互作用，但是二者之间的互作模式与分子机制还不清楚。本项目将利用晶体生物学，生物化学，细胞生物学等手段，在结构与功能上研究FARP2及其与Plexin的互作关系和分子调控机制，为进一步理解Sema-Plexin通路下游信号传导机制提供分子依据。我们之前的结构生物学研究发现FARP2 的DH-PH-PH结构域是一种以自我抑制构象存在的小GTP酶的鸟核苷酸交换因子(GEF)，本项目将进一步探讨如何激活FARP2的GEF活性。", "英文摘要": "英文摘要.The correct wiring of the nervous system relies on the precise axon guidance. During development of the nervous system, axons are guided to their proper targets by sensing a variety of extracellular cues in the local environment. The receptor protein on the neuronal growth cones which is located at the tip of the growing axon, recognizes guidance cues. The signal finally selectively alters the stability of the actin cytoskeleton and microtubules that determine the rate and direction  of   axon  extension.  Semaphorin-Plexin  is  one  of  the  classic ligand/receptor systems involved in this process， and we will focus on FARP2, which is a downstream partner of Plexin A1. FARP2 interacts with Plexin A1 though its N terminal FERM domain, but how they bind is still not clear. We are using  the  combination  of  protein  X-ray  crystallography,  biochemical techniques and cell based assay to study the structure and function of FARP2 and its interaction and regulation with Plexin A1. Our research will help us to understand the molecular regulation mechanisms of downstream signal transduction of Sema-plexin pathway.  C terminal domain DH-PH-PH of FARP2 is an auto-inhibited Guanine nucleotide exchange factor (GEF) based on our previous studies, and we will study how to active GEF activity further.", "负责人职称": "教授"}
+{"项目名称": "Tip49a/Tip49b及其相关复合物的冷冻电镜结构研究", "批准号": "31500606", "项目类别": "青年科学基金项目", "依托单位": "德州学院", "项目负责人": "宋峰", "资助经费(万元)": "20", "批准年度": "2015", "关键词": "冷冻电镜；单颗粒三维重构；蛋白复合物组装", "是否结题": "是", "研究成果(期刊论文;会议论文;著作;奖励;专利)": "4;0;0;0;0", "依托单位ID": "400969", "项目负责人ID": "100181269", "项目类别代码": "630", "申请代码": "C050101", "起止年月": "2016-01至2018-12", "中文摘要": "Tip49a和Tip49b是AAA+超家族的两个蛋白，它们保守地存在于从酵母到人的多个物种中，在细胞内通常以复合物的形式存在。它们在DNA损伤修复、转录调控、snoRNP成熟、染色质重塑等生命活动中发挥重要的调控作用，但迄今为止仍然没有Tip49a/Tip49b全长蛋白相关复合物的结构报道。本研究拟主要应用冷冻电镜单颗粒三维重构技术解析人源Tip49a/Tip49b及其参与形成的两种高级复合物（R2TP、Tip49a/Tip49b-核小体）的高精度三维结构，并结合生化实验确定Tip49a/Tip49b在两种高级复合物中的作用。本项目的研究成果将为理解Tip49a/Tip49b在snoRNP组装（R2TP复合物）和ATP依赖的染色质重塑（Tip49a/Tip49b-核小体复合物）中的工作机制提供可靠的结构信息。", "英文摘要": "Tip49a and Tip49b are two structurally and functionally highly related proteins that belong to the AAA+ (ATPase Associated with diverse cellular Activities) superfamily. They are existed in many species of which ranging from yeast to human. Both Tip49a and Tip49b are conserved components of various multi-subunit complexes, which are linked to a wide range of cellular processes, such as DNA damage response, transcription regulation, snoRNP biogenesis and ATP-dependent chromatin remodeling. Despite their diverse roles, there is no available high resolution structure of full-length Tip49a/Tip49b protein complex. The mainly purpose of our research is to reveal the high resolution structures of dodecameric Tip49a/Tip49b and determine their functions in two larger complexes which containing them, R2TP and Tip49a/Tip49b-nucleosome complex, by using cryo-EM single particle analysis combining with biochemical and biophysical techniques. Our research will provide insights into the structural basis of Tip49a/Tip49b in mediating snoRNP biogenesis(R2TP complex) and ATP-dependent chromatin remodeling(Tip49a/Tip49b-nucleosome complex).", "负责人职称": "教授"}
+{"项目名称": "结核分枝杆菌分枝菌酸合成途径脱水酶HadABC复合物与多种抗结核抑制剂的结构和功能研究", "批准号": "31500607", "项目类别": "青年科学基金项目", "依托单位": "中国科学院上海生命科学研究院", "项目负责人": "李俊", "资助经费(万元)": "20", "批准年度": "2015", "关键词": "结核分枝杆菌；晶体结构；分枝菌酸；脱水酶；药物靶点", "是否结题": "是", "研究成果(期刊论文;会议论文;著作;奖励;专利)": "3;0;0;0;0", "依托单位ID": "201022", "项目负责人ID": "100175031", "项目类别代码": "630", "申请代码": "C050101", "起止年月": "2016-01至2018-12", "中文摘要": "结核病是目前世界上致死率最高、传播范围最广的细菌性疾病。结核分枝杆菌是引发结核病的病原菌，由于耐多药菌株（MDR-TB）和广泛耐药菌株（XDR-TB）的出现，使得现有药物的治疗几乎失效。因此，寻找新的药物靶点以及研究全新作用机制的强力抗结核药物已经成为迫在眉睫的重要任务。由致密的分枝菌酸层构成的细胞壁使得结核分枝杆菌可以逃避免疫攻击和有害物质入侵从而能够存活。脱氢酶HadAB和HadBC是II型分枝菌酸脂链延伸系统（FAS-II）中最晚被发现的两对复合物，也是一线药物异烟肼靶点InhA的下游蛋白。迄今为止，其三维结构和催化机制尚不清楚。本研究项目可以填补这方面的空白，从分子水平上推进其酶活机制的研究；而HadABC与黄酮类抑制剂和抗结核药物Isoxyl、Thiacetazone复合物结构研究将揭示其抗结核的抑制机制，对基于HadABC的抗结核药物开发提供重要线索和可靠的结构生物学基础。", "英文摘要": "Tuberculosis (TB) is the most lethal and widely spread bacterial infectious disease over the world, mainly caused by the pathogenic Mycobacterium tuberculosis (Mtb). Seriously, the emergence of Multi-drug resistant TB (MDR-TB) and extensively drug resistant TB (XDR-TB) make currently used drugs ineffective to cure TB. Therefore, developing novel and effective anti-TB drugs following research of newly found drug targets has already been an urgent and important mission now. Mtb is hard to kill under host immune attack and survives from toxicant invasion because of the dense and hydrophobic mycolic acid layer of cell wall. Both of HadAB and HadBC were the dehydratases, which were the last and latest identified piece of the type II fatty acid synthesis (FAS-II) system, involved in the elongation of mycolic acid chain. The importance of mycolic acid for Mtb makes all the enzymes in this synthesis pathway potential drug targets including HadAB and HadBC. In fact, they were exact downstream enzymes of InhA, an approved target of currently first-line drug isoniazid. So far as we know, there are no crystal structures of HadAB and HadBC reported and the knowledge of catalytic mechanism is unclear as well. Thus, our research will fill in these gaps by deepening our understanding of it enzymatic catalysis from molecular perspective. Our research also aims to unveil inhibition mechanisms by studying the complex structures of HadABC with either flavonoid inhibitors or anti-TB drugs Isoxyl and Thiacetazone, which will lay sound structural basis and provide important clues for the anti-TB drug development.", "负责人职称": "副研究员"}
+{"项目名称": "单颗粒低温透射电镜高分辨率数据收集用支持膜的研究", "批准号": "31500608", "项目类别": "青年科学基金项目", "依托单位": "中国科学院生物物理研究所", "项目负责人": "黄小俊", "资助经费(万元)": "20", "批准年度": "2015", "关键词": "冷冻电镜成像技术；单颗粒三维重构；单颗粒冷冻电镜法", "是否结题": "是", "研究成果(期刊论文;会议论文;著作;奖励;专利)": "0;0;0;0;2", "依托单位ID": "100067", "项目负责人ID": "100172851", "项目类别代码": "630", "申请代码": "C050101", "起止年月": "2016-01至2018-12", "中文摘要": "单颗粒低温透射电镜技术发展至今，最大的瓶颈在于样品制备。而样品制备不可或缺的耗材是透射电镜载网。透射电镜载网（特别是覆在其上的支持膜）的亲水性能，机械性能，导电性能等直接影响着制备样品的质量及数据收集效率。本项目在已自主研制并应用的GIG微阵列碳支持膜的基础上，继续研发更符合实际需要的特定厚度、孔径及孔间距的微阵列支持膜，并以提升支持膜的导电性为目标以开发出第二代的该系列微阵列支持膜。最终将第二代的微阵列支持膜应用到低温透射电镜技术中，降低电子束引发的图像漂移状况，提升单颗粒低温透射电镜成像质量和数据收集效率。", "英文摘要": "Single particle cryo electron microscopy develops very fast these years. The bottle neck of this technique is at sample preparation. Among all those important factors of sample preparation, e.g. protein purity, concentration, rigidity et al., the properties of TEM grid, to be specific, the properties of supporting film on the TEM grid, is essential to preparing a good cryo sample. Hydrophilicity, strong mechanical strength, high conductivity of the supporting film affect the quality of prepared cryo sample and the efficiency of data collection. Based on the self-developed amorphous carbon film with fixed-pattern micro array (brand name GIG), this study aims to develop more suitable supporting films for cryoTEM usage. It includes designing suitable film thickness, hole size, spacing between hole which leads to high efficiency data collection, and increasing the conductivity of the supporting film at liquid nitrogen temperature which reduces the beam induce movement and enhances the quality of cryoEM images.", "负责人职称": "高级工程师"}
+{"项目名称": "干扰素诱导蛋白IFIT/ISG56家族抗病毒功能的结构生物学研究", "批准号": "31500609", "项目类别": "青年科学基金项目", "依托单位": "中国科学院生物物理研究所", "项目负责人": "冯峰", "资助经费(万元)": "20", "批准年度": "2015", "关键词": "IFIT/ISG56家族蛋白；抗病毒；天然免疫", "是否结题": "是", "研究成果(期刊论文;会议论文;著作;奖励;专利)": "1;0;0;0;0", "依托单位ID": "100067", "项目负责人ID": "100218232", "项目类别代码": "630", "申请代码": "C050101", "起止年月": "2016-01至2018-12", "中文摘要": "病原体和干扰素能够诱导ISG56/IFIT 家族蛋白的表达, 它们不仅具有抗病毒作用，而且还参与调节细胞的免疫反应。前期我们在国际上率先解析了该家族成员的晶体结构，并且通过结构信息证实了其抗病毒功能与核酸结合能力有关，但是其背后的分子机制尚不明确。本项目拟通过结构生物学结合细胞生物学的手段，在已获得的研究结果基础上系统地开展ISG56/IFIT 家族各个成员的抗病毒和免疫功能的分子机制的研究，包括比较家族成员之间的晶体结构差异；明确识别和结合核酸的序列和结构的特异性；检测在免疫反应信号通路中相互作用的分子，最终揭示家族各成员选择性激活表达的条件和特异性抗病毒的原因。本项目的研究成果将对宿主抗病毒天然免疫领域的研究以及相应的免疫临床治疗具有重要的理论和现实意义。", "英文摘要": "ISG56/IFIT family proteins，which be induced by interferon and pathogen，have antiviral functions and can regulate cellular immune response. Previously, we first solved the crystal structure of ISG56/IFIT family proteins and discovered that their antiviral functions are related to their ability to recognize nucleotides. However, the molecular mechanism remains unknown. In this project, we aim to reveal the mechanism of ISG56/IFIT proteins using structural and cellular biology methods. Base on the information on crystal structure differences, nucleic acid recognitions, binding partners in innate immune pathway, we try to propose the mechanism of specificity of ISG56/IFIT family proteins' antiviral functions. Our results will deepen people's understanding on innate immune response and provide practical significance on clinical treatment.", "负责人职称": "博士后"}
+{"项目名称": "Wnt信号通路中β-catenin及其细胞核内共激活因子复合物的结构生物学研究", "批准号": "31500610", "项目类别": "青年科学基金项目", "依托单位": "中国科学院生物物理研究所", "项目负责人": "孙伟", "资助经费(万元)": "20", "批准年度": "2015", "关键词": "蛋白质；相互作用；晶体筛选；结构解析；分子置换", "是否结题": "是", "研究成果(期刊论文;会议论文;著作;奖励;专利)": "1;0;0;0;0", "依托单位ID": "100067", "项目负责人ID": "100045287", "项目类别代码": "630", "申请代码": "C050101", "起止年月": "2016-01至2018-12", "中文摘要": "Wnt/β-catenin信号通路的过度激活会导致许多癌症的发生。β-catenin是该通路上的中心效应分子，它的表达上调是这些癌症发生的驱动因素。在细胞核内，多种共激活因子与β-catenin相互作用，共同激活下游肿瘤促进因子如cyclin-D和c-Myc的转录，其中M1型叉头框蛋白（FoxM1）和PCNA相关因子（PAF）就是其中两个。FoxM1促进β-catenin在细胞核内的定位，并可以促进Wnt应激基因的表达，在人类的多种肿瘤（比如神经胶质瘤）中都有过表达。PAF则在结直肠癌和肠干细胞中特异表达。因为β-catenin-FoxM1和β-catenin-PAF复合体的形成是Wnt/β-catenin下游的重要事件，对肿瘤的发生及恶化起重要作用，我们计划对它们开展结构生物学研究，以便阐释相关癌症的发生机理，并为人类癌症治疗提供新的思路。", "英文摘要": "Hyperactivation of the canonical Wnt/β-catenin signaling pathway can cause many types of cancers. β-catenin is the central effector of this signaling pathway, and its upregulation is a driving factor for these cancers. In the nucleus, many coactivators interact with β-catenin, activating transcription of downstream tumor-promoting factors such as cyclin-D and c-Myc. Forhead box protein M1 type (FoxM1) and PCNA-associated factor (PAF) are two β-catenin-specific transcriptional coactivators. FoxM1 promotes β-catenin nuclear localization and induces expression of Wnt responsive genes, and is overexpressed in many cancer types, including glioma. As to PAF, it is specifically expressed in colon cancer and intestine stem cells.  Because formations of β-catenin-FoxM1 and β-catenin-PAF complex are critical events downstream of Wnt/β-catenin signaling pathway, which play vital roles in tumorigenesis and metastasis of many cancers, we embark on investigating the interactions between β-catenin and FoxM1/PAF employing structural biological methods.  We aim to elucidate the molecular mechanism of tumorigenicity and try to provide novel insights into the therapy of human cancers.", "负责人职称": "博士后"}
+{"项目名称": "应用电子顺磁共振技术探究结核分枝杆菌分泌系统内膜蛋白Rv3882c跨膜结构域的结构特征", "批准号": "31500611", "项目类别": "青年科学基金项目", "依托单位": "中国科学院合肥物质科学研究院", "项目负责人": "于璐", "资助经费(万元)": "20", "批准年度": "2015", "关键词": "分枝杆菌分泌系统；膜蛋白；位点特异性自旋标记；电子顺磁共振；结构测定", "是否结题": "是", "研究成果(期刊论文;会议论文;著作;奖励;专利)": "2;0;0;0;0", "依托单位ID": "100212", "项目负责人ID": "100134186", "项目类别代码": "630", "申请代码": "C050101", "起止年月": "2016-01至2018-12", "中文摘要": "结核分枝杆菌的ESX-1分泌系统能使菌体分泌的致病因子、存活因子等蛋白质穿过其高度疏水致密的细胞被膜，对结核分枝杆菌的毒力和存活极为关键。因此，有关ESX-1分泌系统相关组成蛋白的结构分析对于理解结核杆菌感染机制具有非常重要的意义。Rv3882c蛋白是ESX-1分泌系统中一种重要的内膜蛋白，可能与其他组成蛋白共同形成通道类复合物，负责转运底物穿过细胞被膜，但目前其空间结构和确切的生物学功能尚不明确，仍亟待研究。本项目将结合位点特异性自旋标记与电子顺磁共振技术，通过获取Rv3882c蛋白跨膜结构域的运动性信息、易趋性信息以及在膜环境中的取向信息，综合分析得到Rv3882c蛋白跨膜结构域在膜环境中的三维结构模型。本项目的顺利开展，将为Rv3882c蛋白的结构研究提供重要依据，有助于进一步阐明结核分枝杆菌的分泌系统与致病机制，也为应用电子顺磁共振技术研究其他膜蛋白结构提供方法与思路。", "英文摘要": "The ESX-1 secretion system of Mycobacterium tuberculosis serves to secrete proteins, such as virulence factors and survival factors, across its highly hydrophobic and poorly permeable cell envelop, which is crucial for the virulence and survival of Mycobacterium tuberculosis. Therefore, structural investigation on component proteins of ESX-1 secretion system is very important for understanding the infection mechanisms of Mycobacterium tuberculosis. Rv0082c is a very important membrane protein of ESX-1 secretion system and is located on the inner membrane of Mycobacterium tuberculosis. It was predicted that Rv3382c forms a channel-like complex with other proteins and functions to transport the substrates across the mycobacterial cell envelope. However, the structure and function of this protein is still unclear. In this proposal, we are trying to characterize the structure of the transmembrane domain of membrane protein Rv3882c by combing Site Directed Spin Labelling (SDSL) technology and Electron Paramagnetic Resonance (EPR) spectroscopy. The acquired mobility, accessibility and orientation information in membrane will be integrated to derive a three dimensional structural model of the transmembrane domain of Rv3882c. Successful implementation of this project will not only yield valuable information for structural determination of Rv3882c, but also provide deeper insights of the protein secretion system and pathogenic mechanism of Mycobacterium tuberculosis. Also, this project will provide method of using EPR as the tool for structural studies of other membrane proteins.", "负责人职称": "副研究员"}
+{"项目名称": "真核生物mRNA转录出核复合物TREX-1的结构与功能研究", "批准号": "31500612", "项目类别": "青年科学基金项目", "依托单位": "许昌学院", "项目负责人": "苏测洋", "资助经费(万元)": "20", "批准年度": "2015", "关键词": "mRNA转录出核复合物；THO复合物；蛋白质结构生物学；X-射线晶体学；冷冻电镜", "是否结题": "是", "研究成果(期刊论文;会议论文;著作;奖励;专利)": "0;0;0;0;0", "依托单位ID": "400411", "项目负责人ID": "100181698", "项目类别代码": "630", "申请代码": "C050101", "起止年月": "2016-01至2018-12", "中文摘要": "真核生物mRNA转录出核复合物TREX-1广泛存在于从酵母到哺乳动物中，参与mRNA的转录、转录后加工和出核运输等一系列过程。有报道指出，TREX-1复合物组分在很多癌症组织中检测到表达异常。TREX-1复合物在真核生物中保守性较高，酵母源TREX-1复合物由Sub2、Yra1和THO复合物组成，人源TREX-1复合物由Uap56、Yra1以及人源THO复合物组成。目前，缺乏TREX-1复合物的高分辨率三维结构，这极大的阻碍了对其参与pre-mRNA加工分子机理的深入研究。我们之前的研究通过昆虫杆状病毒体外重组表达获得了高纯度的酵母源THO复合物。在此基础上，本项目拟对酵母和人源的TREX-1复合物进行组装与纯化，通过结合蛋白质X射线晶体学和冷冻电镜技术，以期获得TREX-1复合物高分辨率三维结构，并辅以生物化学和细胞生物学技术，研究其组装及参与mRNA出核的分子机制。", "英文摘要": "Eukaryotic mRNA TRanscription/EXport complex-1 (TREX-1 complex) is evolutionarily conserved multi-protein complex from yeast to human, participating in mRNA transcription, post-transcription processing and export. Previous report indicated that different protein component of TREX-1 complex has dysregulated expressed in different cancer specimens. Yeast TREX-1 complex consists Sub2, Yra1 and THO complex, while human TREX-1 complex consists Uap56 (yeast Sub2 homologous protein), Aly (yeast Yra1 homologous protein) and human THO complex. The detail mechanism of how TREX-1 complex participate pre-mRNA maturation and export is still obscurity, due to the miss of high-resolution 3D structural model of TREX-1 complex. In previous study, we get highly purified yeast THO complex through recombinant baculovirus expression system. Based on these, we try to reconstitute yeast and human TREX-1 complex in vivo and in vitro, through protein X-ray crystallography and cyro-EM technology, aim to get high-resolution 3D structure of TREX-1 complex. We also try to use biochemical and cell biology method to investigate the molecular mechanism of TREX-1 assembling and its participation mRNA export.", "负责人职称": "讲师"}
+{"项目名称": "一种新的葡萄糖脱氢酶FAD-GDH的晶体结构与催化机制研究", "批准号": "31560244", "项目类别": "地区科学基金项目", "依托单位": "遵义医科大学", "项目负责人": "杨愈丰", "资助经费(万元)": "40", "批准年度": "2015", "关键词": "", "是否结题": "否", "研究成果(期刊论文;会议论文;著作;奖励;专利)": "0;0;0;0;0", "依托单位ID": "", "项目负责人ID": "", "项目类别代码": "631", "申请代码": "C050101", "起止年月": "2016-01至2019-12", "中文摘要": "", "英文摘要": "", "负责人职称": ""}
+{"项目名称": "高等植物PSII-LHCII超复合物的三维结构研究", "批准号": "31570724", "项目类别": "面上项目", "依托单位": "中国科学院生物物理研究所", "项目负责人": "曹鹏", "资助经费(万元)": "70", "批准年度": "2015", "关键词": "", "是否结题": "否", "研究成果(期刊论文;会议论文;著作;奖励;专利)": "0;0;0;0;0", "依托单位ID": "", "项目负责人ID": "", "项目类别代码": "218", "申请代码": "C050101", "起止年月": "2016-01至2019-12", "中文摘要": "", "英文摘要": "", "负责人职称": ""}
+{"项目名称": "铁吸收调控蛋白Fur的复合物结构和识别机制研究", "批准号": "31570725", "项目类别": "面上项目", "依托单位": "中国农业大学", "项目负责人": "陈忠周", "资助经费(万元)": "65", "批准年度": "2015", "关键词": "", "是否结题": "否", "研究成果(期刊论文;会议论文;著作;奖励;专利)": "0;0;0;0;0", "依托单位ID": "", "项目负责人ID": "", "项目类别代码": "218", "申请代码": "C050101", "起止年月": "2016-01至2019-12", "中文摘要": "", "英文摘要": "", "负责人职称": ""}
+{"项目名称": "中介体核心复合物调控RNA聚合酶II的结构机制研究", "批准号": "31570726", "项目类别": "面上项目", "依托单位": "中国科学技术大学", "项目负责人": "王雪娟", "资助经费(万元)": "60", "批准年度": "2015", "关键词": "", "是否结题": "否", "研究成果(期刊论文;会议论文;著作;奖励;专利)": "0;0;0;0;0", "依托单位ID": "", "项目负责人ID": "", "项目类别代码": "218", "申请代码": "C050101", "起止年月": "2016-01至2019-12", "中文摘要": "", "英文摘要": "", "负责人职称": ""}
+{"项目名称": "基于冷冻电镜的呼肠孤病毒转录的分子机制研究", "批准号": "31570727", "项目类别": "面上项目", "依托单位": "清华大学", "项目负责人": "程凌鹏", "资助经费(万元)": "62", "批准年度": "2015", "关键词": "", "是否结题": "否", "研究成果(期刊论文;会议论文;著作;奖励;专利)": "0;0;0;0;0", "依托单位ID": "", "项目负责人ID": "", "项目类别代码": "218", "申请代码": "C050101", "起止年月": "2016-01至2019-12", "中文摘要": "", "英文摘要": "", "负责人职称": ""}
+{"项目名称": "肺炎链球菌荚膜多糖合成途径的结构酶学", "批准号": "31570728", "项目类别": "面上项目", "依托单位": "中国科学技术大学", "项目负责人": "周丛照", "资助经费(万元)": "62", "批准年度": "2015", "关键词": "", "是否结题": "否", "研究成果(期刊论文;会议论文;著作;奖励;专利)": "0;0;0;0;0", "依托单位ID": "", "项目负责人ID": "", "项目类别代码": "218", "申请代码": "C050101", "起止年月": "2016-01至2019-12", "中文摘要": "", "英文摘要": "", "负责人职称": ""}
+{"项目名称": "核小体水平上组蛋白修饰酶和组蛋白密码识别因子参与表观遗传调控的分子机理研究", "批准号": "31570729", "项目类别": "面上项目", "依托单位": "北京师范大学", "项目负责人": "王占新", "资助经费(万元)": "65", "批准年度": "2015", "关键词": "", "是否结题": "否", "研究成果(期刊论文;会议论文;著作;奖励;专利)": "0;0;0;0;0", "依托单位ID": "", "项目负责人ID": "", "项目类别代码": "218", "申请代码": "C050101", "起止年月": "2016-01至2019-12", "中文摘要": "", "英文摘要": "", "负责人职称": ""}
+{"项目名称": "冷冻电镜数据采集和实时电子显微图像处理技术研究", "批准号": "31570730", "项目类别": "面上项目", "依托单位": "清华大学", "项目负责人": "李雪明", "资助经费(万元)": "70", "批准年度": "2015", "关键词": "", "是否结题": "否", "研究成果(期刊论文;会议论文;著作;奖励;专利)": "0;0;0;0;0", "依托单位ID": "", "项目负责人ID": "", "项目类别代码": "218", "申请代码": "C050101", "起止年月": "2016-01至2019-12", "中文摘要": "", "英文摘要": "", "负责人职称": ""}
+{"项目名称": "核小体组蛋白H4被picNuA4复合物选择性乙酰化的结构基础", "批准号": "31570731", "项目类别": "面上项目", "依托单位": "清华大学", "项目负责人": "陈柱成", "资助经费(万元)": "62", "批准年度": "2015", "关键词": "", "是否结题": "否", "研究成果(期刊论文;会议论文;著作;奖励;专利)": "0;0;0;0;0", "依托单位ID": "", "项目负责人ID": "", "项目类别代码": "218", "申请代码": "C050101", "起止年月": "2016-01至2019-12", "中文摘要": "", "英文摘要": "", "负责人职称": ""}
+{"项目名称": "小分子热休克蛋白的结构与作用机制", "批准号": "31570732", "项目类别": "面上项目", "依托单位": "北京大学", "项目负责人": "尹长城", "资助经费(万元)": "65", "批准年度": "2015", "关键词": "", "是否结题": "否", "研究成果(期刊论文;会议论文;著作;奖励;专利)": "0;0;0;0;0", "依托单位ID": "", "项目负责人ID": "", "项目类别代码": "218", "申请代码": "C050101", "起止年月": "2016-01至2019-12", "中文摘要": "", "英文摘要": "", "负责人职称": ""}
+{"项目名称": "ABC转运蛋白的结构与功能研究", "批准号": "31570733", "项目类别": "面上项目", "依托单位": "清华大学", "项目负责人": "杨茂君", "资助经费(万元)": "65", "批准年度": "2015", "关键词": "", "是否结题": "否", "研究成果(期刊论文;会议论文;著作;奖励;专利)": "0;0;0;0;0", "依托单位ID": "", "项目负责人ID": "", "项目类别代码": "218", "申请代码": "C050101", "起止年月": "2016-01至2019-12", "中文摘要": "", "英文摘要": "", "负责人职称": ""}
+{"项目名称": "细菌外源基因抑制因子的结构与功能研究", "批准号": "31570734", "项目类别": "面上项目", "依托单位": "北京大学", "项目负责人": "夏斌", "资助经费(万元)": "70", "批准年度": "2015", "关键词": "", "是否结题": "否", "研究成果(期刊论文;会议论文;著作;奖励;专利)": "0;0;0;0;0", "依托单位ID": "", "项目负责人ID": "", "项目类别代码": "218", "申请代码": "C050101", "起止年月": "2016-01至2019-12", "中文摘要": "", "英文摘要": "", "负责人职称": ""}
+{"项目名称": "分泌系统内新型激酶的结构和底物识别机制研究", "批准号": "31570735", "项目类别": "面上项目", "依托单位": "北京大学", "项目负责人": "肖俊宇", "资助经费(万元)": "62", "批准年度": "2015", "关键词": "", "是否结题": "否", "研究成果(期刊论文;会议论文;著作;奖励;专利)": "0;0;0;0;0", "依托单位ID": "", "项目负责人ID": "", "项目类别代码": "218", "申请代码": "C050101", "起止年月": "2016-01至2019-12", "中文摘要": "", "英文摘要": "", "负责人职称": ""}
+{"项目名称": "衣原体III型分泌系统结构的低温电镜研究", "批准号": "31570736", "项目类别": "面上项目", "依托单位": "中山大学", "项目负责人": "张勤奋", "资助经费(万元)": "60", "批准年度": "2015", "关键词": "", "是否结题": "否", "研究成果(期刊论文;会议论文;著作;奖励;专利)": "0;0;0;0;0", "依托单位ID": "", "项目负责人ID": "", "项目类别代码": "218", "申请代码": "C050101", "起止年月": "2016-01至2019-12", "中文摘要": "", "英文摘要": "", "负责人职称": ""}
+{"项目名称": "人的SMN复合物识别snRNA调控snRNP装配的结构生物学研究", "批准号": "31570737", "项目类别": "面上项目", "依托单位": "中国科学技术大学", "项目负责人": "许超", "资助经费(万元)": "62", "批准年度": "2015", "关键词": "", "是否结题": "否", "研究成果(期刊论文;会议论文;著作;奖励;专利)": "0;0;0;0;0", "依托单位ID": "", "项目负责人ID": "", "项目类别代码": "218", "申请代码": "C050101", "起止年月": "2016-01至2019-12", "中文摘要": "", "英文摘要": "", "负责人职称": ""}
+{"项目名称": "光合玫瑰菌核心光合复合体的结构与功能研究", "批准号": "31570738", "项目类别": "面上项目", "依托单位": "杭州师范大学", "项目负责人": "徐晓玲", "资助经费(万元)": "62", "批准年度": "2015", "关键词": "", "是否结题": "否", "研究成果(期刊论文;会议论文;著作;奖励;专利)": "0;0;0;0;0", "依托单位ID": "", "项目负责人ID": "", "项目类别代码": "218", "申请代码": "C050101", "起止年月": "2016-01至2019-12", "中文摘要": "", "英文摘要": "", "负责人职称": ""}
+{"项目名称": "神经肽Y受体NPY1R的结构生物学研究", "批准号": "31570739", "项目类别": "面上项目", "依托单位": "中国科学院上海药物研究所", "项目负责人": "吴蓓丽", "资助经费(万元)": "70", "批准年度": "2015", "关键词": "", "是否结题": "否", "研究成果(期刊论文;会议论文;著作;奖励;专利)": "0;0;0;0;0", "依托单位ID": "", "项目负责人ID": "", "项目类别代码": "218", "申请代码": "C050101", "起止年月": "2016-01至2019-12", "中文摘要": "", "英文摘要": "", "负责人职称": ""}
+{"项目名称": "具有新颖催化活性的细胞色素P450酶TxtE和甲基转移酶TleD的晶体结构和功能研究", "批准号": "31570740", "项目类别": "面上项目", "依托单位": "中国科学院上海应用物理研究所", "项目负责人": "郁峰", "资助经费(万元)": "62", "批准年度": "2015", "关键词": "", "是否结题": "否", "研究成果(期刊论文;会议论文;著作;奖励;专利)": "0;0;0;0;0", "依托单位ID": "", "项目负责人ID": "", "项目类别代码": "218", "申请代码": "C050101", "起止年月": "2016-01至2019-12", "中文摘要": "", "英文摘要": "", "负责人职称": ""}
+{"项目名称": "Liprin-α介导的神经突触形成中活性区组装机制的研究", "批准号": "31570741", "项目类别": "面上项目", "依托单位": "南方科技大学", "项目负责人": "魏志毅", "资助经费(万元)": "62", "批准年度": "2015", "关键词": "", "是否结题": "否", "研究成果(期刊论文;会议论文;著作;奖励;专利)": "0;0;0;0;0", "依托单位ID": "", "项目负责人ID": "", "项目类别代码": "218", "申请代码": "C050101", "起止年月": "2016-01至2019-12", "中文摘要": "", "英文摘要": "", "负责人职称": ""}
+{"项目名称": "基于冷冻电镜二十面体对称失配三维重构的腺病毒结构研究", "批准号": "31570742", "项目类别": "面上项目", "依托单位": "湖南师范大学", "项目负责人": "刘红荣", "资助经费(万元)": "62", "批准年度": "2015", "关键词": "", "是否结题": "否", "研究成果(期刊论文;会议论文;著作;奖励;专利)": "0;0;0;0;0", "依托单位ID": "", "项目负责人ID": "", "项目类别代码": "218", "申请代码": "C050101", "起止年月": "2016-01至2019-12", "中文摘要": "", "英文摘要": "", "负责人职称": ""}
+{"项目名称": "糖原代谢关键蛋白质的结构和功能研究", "批准号": "31570743", "项目类别": "面上项目", "依托单位": "中国科学院上海生命科学研究院", "项目负责人": "向嵩", "资助经费(万元)": "60", "批准年度": "2015", "关键词": "", "是否结题": "否", "研究成果(期刊论文;会议论文;著作;奖励;专利)": "0;0;0;0;0", "依托单位ID": "", "项目负责人ID": "", "项目类别代码": "218", "申请代码": "C050101", "起止年月": "2016-01至2019-12", "中文摘要": "", "英文摘要": "", "负责人职称": ""}
+{"项目名称": "蛋白质晶体学结构测定新技术研究", "批准号": "31570744", "项目类别": "面上项目", "依托单位": "中国科学院高能物理研究所", "项目负责人": "董宇辉", "资助经费(万元)": "65", "批准年度": "2015", "关键词": "", "是否结题": "否", "研究成果(期刊论文;会议论文;著作;奖励;专利)": "0;0;0;0;0", "依托单位ID": "", "项目负责人ID": "", "项目类别代码": "218", "申请代码": "C050101", "起止年月": "2016-01至2019-12", "中文摘要": "", "英文摘要": "", "负责人职称": ""}
+{"项目名称": "内吞性胶原蛋白受体Endo180 的结构研究", "批准号": "31570745", "项目类别": "面上项目", "依托单位": "福州大学", "项目负责人": "袁彩", "资助经费(万元)": "62", "批准年度": "2015", "关键词": "", "是否结题": "否", "研究成果(期刊论文;会议论文;著作;奖励;专利)": "0;0;0;0;0", "依托单位ID": "", "项目负责人ID": "", "项目类别代码": "218", "申请代码": "C050101", "起止年月": "2016-01至2019-12", "中文摘要": "", "英文摘要": "", "负责人职称": ""}
+{"项目名称": "线粒体解偶联蛋白UCP1的结构和功能解析", "批准号": "31570746", "项目类别": "面上项目", "依托单位": "中国科学院上海生命科学研究院", "项目负责人": "周界文", "资助经费(万元)": "65", "批准年度": "2015", "关键词": "", "是否结题": "否", "研究成果(期刊论文;会议论文;著作;奖励;专利)": "0;0;0;0;0", "依托单位ID": "", "项目负责人ID": "", "项目类别代码": "218", "申请代码": "C050101", "起止年月": "2016-01至2019-12", "中文摘要": "", "英文摘要": "", "负责人职称": ""}
+{"项目名称": "参与基因表达转录后调控的重要蛋白质-RNA复合物的结构与功能研究", "批准号": "31570747", "项目类别": "面上项目", "依托单位": "中国科学院生物物理研究所", "项目负责人": "刘超培", "资助经费(万元)": "60", "批准年度": "2015", "关键词": "", "是否结题": "否", "研究成果(期刊论文;会议论文;著作;奖励;专利)": "0;0;0;0;0", "依托单位ID": "", "项目负责人ID": "", "项目类别代码": "218", "申请代码": "C050101", "起止年月": "2016-01至2019-12", "中文摘要": "", "英文摘要": "", "负责人职称": ""}
+{"项目名称": "磷脂酰肌醇合成酶的结构与功能", "批准号": "31570748", "项目类别": "面上项目", "依托单位": "中国科学院上海生命科学研究院", "项目负责人": "李典范", "资助经费(万元)": "62", "批准年度": "2015", "关键词": "", "是否结题": "否", "研究成果(期刊论文;会议论文;著作;奖励;专利)": "0;0;0;0;0", "依托单位ID": "", "项目负责人ID": "", "项目类别代码": "218", "申请代码": "C050101", "起止年月": "2016-01至2019-12", "中文摘要": "", "英文摘要": "", "负责人职称": ""}
+{"项目名称": "负链RNA病毒聚合酶的结构和功能机制研究", "批准号": "31530015", "项目类别": "重点项目", "依托单位": "中国科学院生物物理研究所", "项目负责人": "刘迎芳", "资助经费(万元)": "292", "批准年度": "2015", "关键词": "", "是否结题": "否", "研究成果(期刊论文;会议论文;著作;奖励;专利)": "0;0;0;0;0", "依托单位ID": "", "项目负责人ID": "", "项目类别代码": "220", "申请代码": "C050101", "起止年月": "2016-01至2020-12", "中文摘要": "", "英文摘要": "", "负责人职称": ""}
+{"项目名称": "染色体的结构与功能研究", "批准号": "31525007", "项目类别": "国家杰出青年科学基金", "依托单位": "上海交通大学", "项目负责人": "雷鸣", "资助经费(万元)": "350", "批准年度": "2015", "关键词": "", "是否结题": "否", "研究成果(期刊论文;会议论文;著作;奖励;专利)": "0;0;0;0;0", "依托单位ID": "", "项目负责人ID": "", "项目类别代码": "429", "申请代码": "C050101", "起止年月": "2016-01至2020-12", "中文摘要": "", "英文摘要": "", "负责人职称": ""}
diff --git a/examples/demo.json b/examples/demo.json
index 090dfcd..f4d8689 100644
--- a/examples/demo.json
+++ b/examples/demo.json
@@ -1,6 +1,5 @@
 [
   {
-    "h": "",
     "项目名称": "脱敏态GluA2配体结合域LBD二聚体系综结构及其调控的研究",
     "批准号": "31500595",
     "项目类别": "青年科学基金项目",
@@ -21,7 +20,6 @@
     "负责人职称": "教授"
   },
   {
-    "h": "",
     "项目名称": "帕金森病致病蛋白LRRK2的ROC结构域GTP水解抑制机制与结构生物学研究",
     "批准号": "31500596",
     "项目类别": "青年科学基金项目",
@@ -42,7 +40,6 @@
     "负责人职称": "副教授"
   },
   {
-    "h": "",
     "项目名称": "线性泛素链组装复合物(LUBAC)的调节机制研究",
     "批准号": "31500597",
     "项目类别": "青年科学基金项目",
@@ -63,7 +60,6 @@
     "负责人职称": "副研究员"
   },
   {
-    "h": "",
     "项目名称": "转录因子CcmR调控蓝细菌碳浓缩机制的结构生物学基础",
     "批准号": "31500598",
     "项目类别": "青年科学基金项目",
@@ -84,7 +80,6 @@
     "负责人职称": "博士后"
   },
   {
-    "h": "",
     "项目名称": "三维超分辨技术研究细胞核孔复合物的选择性屏障分布",
     "批准号": "31500599",
     "项目类别": "青年科学基金项目",
@@ -105,7 +100,6 @@
     "负责人职称": "研究员"
   },
   {
-    "h": "",
     "项目名称": "成肌细胞融合蛋白myomaker的结构基础与作用机理",
     "批准号": "31500600",
     "项目类别": "青年科学基金项目",
@@ -126,7 +120,6 @@
     "负责人职称": "博士后"
   },
   {
-    "h": "",
     "项目名称": "布氏锥虫中参与基因转录调控的PAF1复合物的结构和功能研究",
     "批准号": "31500601",
     "项目类别": "青年科学基金项目",
@@ -147,7 +140,6 @@
     "负责人职称": "副研究员"
   },
   {
-    "h": "",
     "项目名称": "铜绿微囊藻气囊蛋白的结构和功能研究",
     "批准号": "31500602",
     "项目类别": "青年科学基金项目",
@@ -168,7 +160,6 @@
     "负责人职称": "博士后"
   },
   {
-    "h": "",
     "项目名称": "膜环境对膜蛋白DAGK结构与功能的影响",
     "批准号": "31500603",
     "项目类别": "青年科学基金项目",
@@ -189,7 +180,6 @@
     "负责人职称": "助理研究员"
   },
   {
-    "h": "",
     "项目名称": "与ALS/FTD相关联的C9orf72六核苷酸重复扩增形成G-四链体的结构研究",
     "批准号": "31500604",
     "项目类别": "青年科学基金项目",
@@ -210,7 +200,6 @@
     "负责人职称": "副研究员"
   },
   {
-    "h": "",
     "项目名称": "Sema-Plexin信号通路中FARP2的结构与功能研究",
     "批准号": "31500605",
     "项目类别": "青年科学基金项目",
@@ -231,7 +220,6 @@
     "负责人职称": "教授"
   },
   {
-    "h": "",
     "项目名称": "Tip49a/Tip49b及其相关复合物的冷冻电镜结构研究",
     "批准号": "31500606",
     "项目类别": "青年科学基金项目",
@@ -252,7 +240,6 @@
     "负责人职称": "教授"
   },
   {
-    "h": "",
     "项目名称": "结核分枝杆菌分枝菌酸合成途径脱水酶HadABC复合物与多种抗结核抑制剂的结构和功能研究",
     "批准号": "31500607",
     "项目类别": "青年科学基金项目",
@@ -273,7 +260,6 @@
     "负责人职称": "副研究员"
   },
   {
-    "h": "",
     "项目名称": "单颗粒低温透射电镜高分辨率数据收集用支持膜的研究",
     "批准号": "31500608",
     "项目类别": "青年科学基金项目",
@@ -294,7 +280,6 @@
     "负责人职称": "高级工程师"
   },
   {
-    "h": "",
     "项目名称": "干扰素诱导蛋白IFIT/ISG56家族抗病毒功能的结构生物学研究",
     "批准号": "31500609",
     "项目类别": "青年科学基金项目",
@@ -315,7 +300,6 @@
     "负责人职称": "博士后"
   },
   {
-    "h": "",
     "项目名称": "Wnt信号通路中β-catenin及其细胞核内共激活因子复合物的结构生物学研究",
     "批准号": "31500610",
     "项目类别": "青年科学基金项目",
@@ -336,7 +320,6 @@
     "负责人职称": "博士后"
   },
   {
-    "h": "",
     "项目名称": "应用电子顺磁共振技术探究结核分枝杆菌分泌系统内膜蛋白Rv3882c跨膜结构域的结构特征",
     "批准号": "31500611",
     "项目类别": "青年科学基金项目",
@@ -357,7 +340,6 @@
     "负责人职称": "副研究员"
   },
   {
-    "h": "",
     "项目名称": "真核生物mRNA转录出核复合物TREX-1的结构与功能研究",
     "批准号": "31500612",
     "项目类别": "青年科学基金项目",
@@ -378,7 +360,6 @@
     "负责人职称": "讲师"
   },
   {
-    "h": "",
     "项目名称": "一种新的葡萄糖脱氢酶FAD-GDH的晶体结构与催化机制研究",
     "批准号": "31560244",
     "项目类别": "地区科学基金项目",
@@ -399,7 +380,6 @@
     "负责人职称": ""
   },
   {
-    "h": "",
     "项目名称": "高等植物PSII-LHCII超复合物的三维结构研究",
     "批准号": "31570724",
     "项目类别": "面上项目",
@@ -420,7 +400,6 @@
     "负责人职称": ""
   },
   {
-    "h": "",
     "项目名称": "铁吸收调控蛋白Fur的复合物结构和识别机制研究",
     "批准号": "31570725",
     "项目类别": "面上项目",
@@ -441,7 +420,6 @@
     "负责人职称": ""
   },
   {
-    "h": "",
     "项目名称": "中介体核心复合物调控RNA聚合酶II的结构机制研究",
     "批准号": "31570726",
     "项目类别": "面上项目",
@@ -462,7 +440,6 @@
     "负责人职称": ""
   },
   {
-    "h": "",
     "项目名称": "基于冷冻电镜的呼肠孤病毒转录的分子机制研究",
     "批准号": "31570727",
     "项目类别": "面上项目",
@@ -483,7 +460,6 @@
     "负责人职称": ""
   },
   {
-    "h": "",
     "项目名称": "肺炎链球菌荚膜多糖合成途径的结构酶学",
     "批准号": "31570728",
     "项目类别": "面上项目",
@@ -504,7 +480,6 @@
     "负责人职称": ""
   },
   {
-    "h": "",
     "项目名称": "核小体水平上组蛋白修饰酶和组蛋白密码识别因子参与表观遗传调控的分子机理研究",
     "批准号": "31570729",
     "项目类别": "面上项目",
@@ -525,7 +500,6 @@
     "负责人职称": ""
   },
   {
-    "h": "",
     "项目名称": "冷冻电镜数据采集和实时电子显微图像处理技术研究",
     "批准号": "31570730",
     "项目类别": "面上项目",
@@ -546,7 +520,6 @@
     "负责人职称": ""
   },
   {
-    "h": "",
     "项目名称": "核小体组蛋白H4被picNuA4复合物选择性乙酰化的结构基础",
     "批准号": "31570731",
     "项目类别": "面上项目",
@@ -567,7 +540,6 @@
     "负责人职称": ""
   },
   {
-    "h": "",
     "项目名称": "小分子热休克蛋白的结构与作用机制",
     "批准号": "31570732",
     "项目类别": "面上项目",
@@ -588,7 +560,6 @@
     "负责人职称": ""
   },
   {
-    "h": "",
     "项目名称": "ABC转运蛋白的结构与功能研究",
     "批准号": "31570733",
     "项目类别": "面上项目",
@@ -609,7 +580,6 @@
     "负责人职称": ""
   },
   {
-    "h": "",
     "项目名称": "细菌外源基因抑制因子的结构与功能研究",
     "批准号": "31570734",
     "项目类别": "面上项目",
@@ -630,7 +600,6 @@
     "负责人职称": ""
   },
   {
-    "h": "",
     "项目名称": "分泌系统内新型激酶的结构和底物识别机制研究",
     "批准号": "31570735",
     "项目类别": "面上项目",
@@ -651,7 +620,6 @@
     "负责人职称": ""
   },
   {
-    "h": "",
     "项目名称": "衣原体III型分泌系统结构的低温电镜研究",
     "批准号": "31570736",
     "项目类别": "面上项目",
@@ -672,7 +640,6 @@
     "负责人职称": ""
   },
   {
-    "h": "",
     "项目名称": "人的SMN复合物识别snRNA调控snRNP装配的结构生物学研究",
     "批准号": "31570737",
     "项目类别": "面上项目",
@@ -693,7 +660,6 @@
     "负责人职称": ""
   },
   {
-    "h": "",
     "项目名称": "光合玫瑰菌核心光合复合体的结构与功能研究",
     "批准号": "31570738",
     "项目类别": "面上项目",
@@ -714,7 +680,6 @@
     "负责人职称": ""
   },
   {
-    "h": "",
     "项目名称": "神经肽Y受体NPY1R的结构生物学研究",
     "批准号": "31570739",
     "项目类别": "面上项目",
@@ -735,7 +700,6 @@
     "负责人职称": ""
   },
   {
-    "h": "",
     "项目名称": "具有新颖催化活性的细胞色素P450酶TxtE和甲基转移酶TleD的晶体结构和功能研究",
     "批准号": "31570740",
     "项目类别": "面上项目",
@@ -756,7 +720,6 @@
     "负责人职称": ""
   },
   {
-    "h": "",
     "项目名称": "Liprin-α介导的神经突触形成中活性区组装机制的研究",
     "批准号": "31570741",
     "项目类别": "面上项目",
@@ -777,7 +740,6 @@
     "负责人职称": ""
   },
   {
-    "h": "",
     "项目名称": "基于冷冻电镜二十面体对称失配三维重构的腺病毒结构研究",
     "批准号": "31570742",
     "项目类别": "面上项目",
@@ -798,7 +760,6 @@
     "负责人职称": ""
   },
   {
-    "h": "",
     "项目名称": "糖原代谢关键蛋白质的结构和功能研究",
     "批准号": "31570743",
     "项目类别": "面上项目",
@@ -819,7 +780,6 @@
     "负责人职称": ""
   },
   {
-    "h": "",
     "项目名称": "蛋白质晶体学结构测定新技术研究",
     "批准号": "31570744",
     "项目类别": "面上项目",
@@ -840,7 +800,6 @@
     "负责人职称": ""
   },
   {
-    "h": "",
     "项目名称": "内吞性胶原蛋白受体Endo180 的结构研究",
     "批准号": "31570745",
     "项目类别": "面上项目",
@@ -861,7 +820,6 @@
     "负责人职称": ""
   },
   {
-    "h": "",
     "项目名称": "线粒体解偶联蛋白UCP1的结构和功能解析",
     "批准号": "31570746",
     "项目类别": "面上项目",
@@ -882,7 +840,6 @@
     "负责人职称": ""
   },
   {
-    "h": "",
     "项目名称": "参与基因表达转录后调控的重要蛋白质-RNA复合物的结构与功能研究",
     "批准号": "31570747",
     "项目类别": "面上项目",
@@ -903,7 +860,6 @@
     "负责人职称": ""
   },
   {
-    "h": "",
     "项目名称": "磷脂酰肌醇合成酶的结构与功能",
     "批准号": "31570748",
     "项目类别": "面上项目",
@@ -924,7 +880,6 @@
     "负责人职称": ""
   },
   {
-    "h": "",
     "项目名称": "负链RNA病毒聚合酶的结构和功能机制研究",
     "批准号": "31530015",
     "项目类别": "重点项目",
@@ -945,7 +900,6 @@
     "负责人职称": ""
   },
   {
-    "h": "",
     "项目名称": "染色体的结构与功能研究",
     "批准号": "31525007",
     "项目类别": "国家杰出青年科学基金",
diff --git a/examples/demo.pkl b/examples/demo.pkl
index b2ea100..132cdbf 100644
Binary files a/examples/demo.pkl and b/examples/demo.pkl differ
diff --git a/examples/demo.tsv b/examples/demo.tsv
index ec9c40d..5ffa6f5 100644
--- a/examples/demo.tsv
+++ b/examples/demo.tsv
@@ -1,47 +1,47 @@
-h	项目名称	批准号	项目类别	依托单位	项目负责人	资助经费(万元)	批准年度	关键词	是否结题	研究成果(期刊论文;会议论文;著作;奖励;专利)	依托单位ID	项目负责人ID	项目类别代码	申请代码	起止年月	中文摘要	英文摘要	负责人职称
-	脱敏态GluA2配体结合域LBD二聚体系综结构及其调控的研究	31500595	青年科学基金项目	浙江大学	刘主	20	2015	谷氨酸受体；脱敏；顺磁核磁共振；小角X光散射；蛋白质系综结构	是	2;0;0;0;0	100152	100145756	630	C050101	2016-01至2018-12	研究蛋白质系综结构及分布比例使我们了解蛋白质如何行使功能。离子型谷氨酸受体2（GluA2）参与脑内重要的生理和病理过程。研究表明，GluA2为二聚—二聚组成的四聚体，其配体结合域（LBD）二聚体结构的变化对GluA2的配体门控至关重要。由于GluA2的LBD二聚作用极弱（KD值约为6mM），因此对其结构研究极少。最近我们实验发现，在脱敏条件下，LBD的瞬态二聚体存在多种构象。为解析脱敏态LBD二聚体原子分辨率的系综结构及分布比例，本项目拟采用化学交联质谱分析的方法获得低分辨率的系综构象和分布，同时运用顺磁弛豫增强的液体核磁共振技术解析原子分辨的系综结构，并联合小角X光散射以计算各构象比例。基于LBD二聚体的结构，我们将突变界面关键位点，结合电生理，阐明全长GluA2脱敏过程与脱敏态LBD二聚体系综结构的构效关系。据此，我们将从脱敏态LBD二聚体结构动态变化的角度揭示GluA2的脱敏机制。	Depiction of protein ensemble structure has allowed us to understand how the protein fulfills its function. Ionic glutamate acceptor 2 (GluA2) is involved in many important physiological and pathological processes in the brain. GluA2 is tetrameric (dimer of dimer), and its ligand binding domain (LBD) dimer plays a key role in the ligand gating of GluA2. As the LBD only weakly dimerizes by itself, there has been few studies on the ensemble structure of LBD dimer. We found that the LBD dimer adopts an array of relative orientations as the GluA2 shifts into the desensitized state. We thus propose to determine the ensemble structure of LBD dimer. We will use the CXMS (chemical cross-linking of proteins coupled with mass spectrometry analysis) analysis to obtain a low-resolution picture. Conjointly, we will use PRE (paramagnetic relaxation enhancement) NMR to further characterize the ensemble structure of LBD dimer, and use SAXS (small-angle x-ray scattering) to assess the relative populations of each conformational state. Based on the structural characterization, we will mutate key interfacial residues that may perturb the ensemble structure of LBD dimer, which will be confirmed by electrophysiological analyses. Together, we will illustrate how the structural change of LBD dimer accompanies the desensitization of GluA2. If funded and successfully carried out, the project will provide the structural basis for exquisite pharmacological modulation of GluA2 function.	教授
-	帕金森病致病蛋白LRRK2的ROC结构域GTP水解抑制机制与结构生物学研究	31500596	青年科学基金项目	南京理工大学	廖静伶	20	2015	富亮氨酸重复激酶2；ROC结构域；GTP水解活性；结构功能学；帕金森病	是	2;0;0;0;0	100468	100118874	630	C050101	2016-01至2018-12	帕金森病是与年龄密切相关的神经退行性疾病之一。LRRK2基因是目前为止突变率最高的帕金森病致病基因，主要表现在LRRK2蛋白激酶活性的异常增高，但其具体生物功能及致病机制仍不明确。深入研究LRRK2蛋白正常生理功能及基因突变的致病机制将为研究帕金森病治疗策略提供分子机制水平的依据。LRRK2蛋白除了具有激酶活性以外，还拥有GTP水解酶活性，该GTP水解酶活性对激酶活性有调节作用，揭示LRRK2蛋白存在分子内调节机制。LRRK2蛋白特有的生化特征使其成为帕金森病非常有希望的治疗靶点。申请者将运用X射线蛋白晶体学，生物化学及生物物理学方法，通过解析LRRK2蛋白中的ROC结构域晶体结构及GTP水解抑制机制来阐明基因突变的致病机理，为新的通过调控GTP水解酶活性来降低LRRK2的激酶活性的方法提供理论依据。	Parkinson’s disease (PD) is a devastating neurological condition that ravages people’s quality of life as it progresses from the subtle loss of muscular coordination, to severe physical and mental disability, to eventual death. There is no cure and no available treatments to stop this disease progression. Today, mutations in LRRK2 are the most prevalent known genetic causes of Parkinson’s disease, for both familial and sporadic cases. In spite of the intensive efforts over the past decade, the molecular role of LRRK2 in disease pathogenesis, its function, and the effects of disease-causing mutations remain unknown. Understanding the underlying mechanism of LRRK2 normal function and how it is affected by the disease-associated mutations will reveal novel mechanism-based therapeutic strategies. In addition to LRRK2 being associated with PD and being the most promising drug target for the disease, LRRK2 is an immensely intriguing protein, in that it has two enzymatic activities (GTPase activity and Kinase activity) that, together with other non-enzymatic domains, potentially represent a unique example of an intramolecular signaling system. The concept of the Roc GTPase domain functioning as a molecular switch regulating the overall activity of LRRK2 is conceptually interesting from a biochemical perspective, and it is the key to LRRK2’s normal function and disease process. In addition to the relatively wide prevalence of LRRK2 in PD, it is the most attractive target for drug discovery, because over-activation of its kinase activity is linked to disease pathogenesis, and it is an enzyme with active sites well suited for binding potential drugs. Indeed, LRRK2 kinase activity was effectively inhibited by broad kinase inhibitors that compete for ATP in the ATP-binding pocket. However, their translation into the clinic has been difficult due to adverse effects. Various potential alternative strategies are being considered, including targeting the Roc domain. This proposed study seeks to define the structures of ROC domain and its mutants to understand the GTP hydrolysis mechanism and mutations pathogenesis by using X-ray diffraction crystallography, protein biochemistry and biophysics approaches, which could provide insight into locations on LRRK2 structures that are suitable for mechanism-based drug discovery.	副教授
-	线性泛素链组装复合物(LUBAC)的调节机制研究	31500597	青年科学基金项目	中国科学院上海有机化学研究所	刘建平	20	2015	蛋白质复合物；X射线晶体衍射；泛素化；肿瘤坏死因子TNFα；细胞死亡	是	4;0;0;0;0	400014	100193226	630	C050101	2016-01至2018-12	线性泛素化是一类广泛参与炎症和先天免疫的新型泛素化修饰。迄今唯一的线性泛素链E3连接酶LUBAC复合物由调节亚基Sharpin、HOIL1和催化亚基HOIP组成。单独的HOIP处于自抑制状态，但可以被Sharpin或HOIL1激活。然而，HOIP的自抑制和激活、与Sharpin的相互作用机制仍然未知。Sharpin缺失小鼠表现出多器官炎症和TNFα通路异常。为了阐明LUBAC复合物的调控机制，本申请计划解析自抑制和激活状态的HOIP催化核心片段，以及Sharpin/HOIP复合物的结构，揭示HOIP的自抑制和激活机制，并设计点突变解除自抑制或者破坏Sharpin对HOIP的激活，研究相应突变体对细胞死亡或RIP1线性泛素化的影响，以检验我们的假说：Sharpin/HOIP复合物对RIP1的线性泛素化决定了TNFα通路的最终效应——炎症或细胞死亡。现有工作进展为实现上述目标奠定了坚实的基础。	Linear ubiquitination, a recently discovered novel type of ubiquitination, is extensively involved in numerous signaling pathways related to inflammation and innate immune. Linear ubiquitin chain assembly complex (LUBAC) is the sole identified E3 ubiquitin ligase that catalyzes the formation of linear poly-ubiquitin chain. It consists of two regulatory subunits Sharpin and HOIL1 as well as one catalytic subunit HOIP. The isolated HOIP is in an auto-inhibited state, but it can be activated by Sharpin or HOIL1 to sufficiently promote the linear ubiquitination of target substrates. However, the molecular mechanisms underlying the the auto-inhibition of HOIP, its activation by Sharpin or HOIL1, and the interaction between HOIP and Sharpin are largely unknown. Previous studies indicated that loss of Sharpin in the mouse caused immunodeficiency and multi-organ inflammation, and severely inhibited the linear ubiquitination of TNFα receptor signaling complex. Based on these findings, we propose a hypothesis: the linear ubiquitination level of RIP1 catalyzed by Sharpin/HOIP complex determines the outcome of TNFα signaling—inflammation or cell death. To further understand the regulatory mechanism of LUBAC complex, we aimed to solve the structures of the catalytic fragment of HOIP either in auto-inhibited or in activated states as well as the Sharpin/HOIP complex, thereby to uncover the auto-inhibition and activation mechanism of HOIP. Based on the solved structures, we will design point mutations to specifically disrupt the auto-inhibition or the trans-activation of HOIP mediated by Sharpin; we will further test our hypothesis by assessing the impact of these mutations on the linear ubiquitination level of RIP1 and the TNFα induced cell death. Our current research progress has laid the foundation for us to pursue the scientific goals in this proposal.	副研究员
-	转录因子CcmR调控蓝细菌碳浓缩机制的结构生物学基础	31500598	青年科学基金项目	中国科学技术大学	成望	20	2015	蓝藻；碳浓缩机制；转录调控；晶体结构；异构效应	是	1;0;0;0;0	200654	100047316	630	C050101	2016-01至2018-12	蓝细菌是被广泛用于光合作用和碳浓缩机制(CO2-concentrating mechanism, CCM)研究的重要模式生物。CcmR是集胞藻PCC6803中的一个调控碳浓缩机制的全局性转录因子，在低碳信号下解除对CCM相关基因的抑制，引起表达上调，促进CO2的吸收，保证光合作用的顺利进行。我们将以CcmR apo-form四聚体晶体结构为基础，综合利用生物信息学、生物化学、分子生物学以及结构生物学手段，对CcmR与DNA和/或信号分子的相互作用及其二元和三元晶体结构进行系统研究，以期揭示CcmR的别构机理，并基于CcmR特异性识别的DNA序列鉴定其调控的下游基因网络。该项目将阐明CcmR的调控碳浓缩机制的结构基础，有望为生态平衡和农业生产提供理论指导。	Cyanobacterium is an ideal model for studying the photosynthesis and CO2-concentration mechanism (CCM). The transcriptional factor CcmR was first identified in the cyanobacterium Synechocystis sp. PCC6803. It serves as a global controller to increase the expression of CCM related genes, which are suppressed at a high Ci concentration, thus augmenting the uptake of CO2 for the efficacy photosynthesis. Based on our previously determined crystal structure of the apo-form CcmR tetramer, we will systematically investigate the interactions of CcmR with the putative allosteric molecule and its binding DNA, by combining the methodologies of bioinformatics, biochemistry, molecular biology and structural biology. The findings will enable us to elucidate the CcmR allosteric mechanism, and to identify the gene network under the control of CcmR. This project will provide insights into the CCM regulated by CcmR, and might be helpful for guiding the ecological balance control and agricultural production in the future.	博士后
-	三维超分辨技术研究细胞核孔复合物的选择性屏障分布	31500599	青年科学基金项目	复旦大学	马炯	21	2015	细胞核孔复合物；FG屏障；单分子；超分辨显微镜；核孔传输	是	9;0;0;0;0	201361	100162892	630	C050101	2016-01至2018-12	细胞核孔复合物（NPC）是真核细胞中连接细胞质和细胞核之间的选择性双向通道。由富含苯丙氨酸-甘氨酸（FG）氨基酸片段的自然非折叠蛋白构成的FG-屏障,选择性地调控基因相关物质,按照被动运输或者主动介入运输的方式进出细胞核。然而，核孔内FG屏障间的相互作用以及分布状况仍然是极具争议的重要科学问题。本项目将基于申请人发明的单点斜入射激发快速超分辨显微镜技术，研究核孔传输蛋白或FG-蛋白片段与FG屏障反应的三维分布图像，从而获得FG-屏障在细胞核孔内完整的分布情况。另外,进一步检测核孔传输蛋白对FG屏障的分布影响，讨论核孔传输的自调控机制。还将从不同传输蛋白或FG-片段在传输过程中的竞争效果，讨论FG屏障对各类基因相关物质传输的优先顺序。最终，完整的三维FG屏障将对核孔蛋白缺失相关的白血病、阿尔兹海默症的致病机制，以及各种类病毒的侵入机制等核孔相关病理机制或基因治疗提供信息。	The nuclear pore complexes (NPCs) selectively mediate the bidirectional trafficking of macromolecules between the cytoplasm and the nucleus in eukaryotic cells. The selective barrier formed by natively unfolded phenylalanine-glycine (FG) nucleoporins (Nups) inside the NPC allows for passive and facilitated transport through the NPC. However, the interactions that form the FG-barrier and their spatial distribution in the NPC remain unresolved. Based on the single-point edge-excitation sub-diffusion (SPEED) microscopy techniques, the applicant's invention, three-dimensionally map the interaction distributions between the fluorescent transport receptors (TRs) or FG-fragment and FG barrier. Then, we obtain fully information of the FG-barrier distribution in the NPC. The conformation change of the FG-barrier by TRs would be discussed as self-regulating mechanism of nucleocytoplasmic transport. Also from the competitive effects during different FG-fragments and transport proteins during the transport discuss priorities for the various gene related transport. Finally，the complete three-dimensional FG-barrier distribution will provide information with leukemia, Alzheimer's disease pathogenesis, as well as various types of viruses invade mechanisms for NPC related pathological mechanism or gene therapy.	研究员
-	成肌细胞融合蛋白myomaker的结构基础与作用机理	31500600	青年科学基金项目	清华大学	龚德顺	9	2015	膜蛋白；均一性；晶体筛选；结构解析；晶体结构	是	0;0;0;0;0	201260	100177698	630	C050101	2016-01至2016-12	Myomaker是新发现的一种可以直接调控成肌细胞融合和肌肉再生的蛋白，这是哺乳动物细胞中唯一一个被鉴定的肌肉特异性的调节蛋白。它促进成肌细胞融合以及肌肉再生的活性为受伤后的肌肉再生提供了新的机会，为肌肉性疾病的治疗提供了新的思路。然而，目前对其发挥功能的分子机理仍然一无所知。本项目拟从结构生物学的角度出发，解析其晶体结构，揭示其分子作用机理。	Myomaker, a new discovered myoblast fusion activator, which is the only identified muscle-specific protein that directly regulates myoblast fusion and muscle regeneration in mammals. These activities of myomaker provide new opportunities for muscle regeneration and new strategies for therapy of muscle diseases. However, the molecular mechanism of myomaker is still in the dark. The aim of this project is to determinate the crystal structure of myomaker and provide new insights into the functional mechanism of myomaker.	博士后
-	布氏锥虫中参与基因转录调控的PAF1复合物的结构和功能研究	31500601	青年科学基金项目	中国科学技术大学	廖善晖	20	2015	PAF1复合物；转录调控；布氏锥虫；蛋白质结构；蛋白质相互作用	是	11;0;0;0;1	200654	100186764	630	C050101	2016-01至2018-12	真核生物基因转录的调控在时间和空间上都具有很高的复杂度，细胞内基因转录调节的异常与各类疾病密切相关。在研究转录调节的过程中，大量RNA聚合酶相关蛋白复合体被报道，其中PAF1复合物（RNA polymerase II associated factor complex, PAF1C）就是最近发现的一种。PAF1复合物含有至少 5个不同的蛋白亚基，能够协同其他的转录因子及组蛋白修饰酶来调控转录过程。锥虫是一类单细胞真核原生生物，能够引起多种锥虫病。目前在布氏锥虫属中发现的PAF1复合体组成与高等真核生物不完全保守，可能暗示了布氏锥虫特有的基因转录调节方式。本项研究将结合结构生物学和细胞生物学方法，研究布氏锥虫中PAF1复合物的结构及其在基因转录调控中的作用。本研究不仅将丰富我们对布氏锥虫PAF1复合物和基因转录调控的认识，对于我们了解真核生物PAF1复合物和基因转录调控的进化也具有重要意义。	Eukaryotic gene transcription regulation is extremely complex in space and time. Any defect of transcription process is closely related to a variety of diseases. Many protein complexes have been reported during the study of transcription regulation, PAF1C (RNA polymerase II associated factor 1 complex) is such a complex discovered recently. PAF1C, contains at least 5 subunits. It participates in gene transcription regulation cooperatively with other transcription factors and histone modification enzymes. Trypanosomatids, the causative pathogens of trypanosomiasis, are a group of unicellular protozoa. The compositions of PAF1C of Trypanosoma brucei (T. brucei) is not fully conserved with that from higher eukaryotes, which may imply species-specific regulation pathway of gene transcription. Here, we are trying to explore the structure of PAF1C and its role in gene transcription regulation in T. brucei, by combining the techniques of structural biology and cell biology. This study will not only enrich our knowledge of PAF1C’s role in transcription regulation in T. brucei, but also has important implications for our understanding of the evolution of eukaryotic PAF1 complex and gene transcription regulation.	副研究员
-	铜绿微囊藻气囊蛋白的结构和功能研究	31500602	青年科学基金项目	中国科学技术大学	代亚男	20	2015	铜绿微囊藻；气囊；气囊蛋白；晶体结构；结构蛋白	是	0;0;0;0;0	200654	100047317	630	C050101	2016-01至2018-12	铜绿微囊藻是一种单细胞浮游蓝藻，能大量产生气囊，营养丰富时在淡水水体表面聚集暴发水华。气囊是一种完全由蛋白质组成的中空、充满气体的惰性结构。气囊为藻细胞提供浮力，使其自行调节在自然水体中的垂直位置，漂浮到氧气和光照都适宜的位置以利于自身生长和生境殖民化。气囊不仅是铜绿微囊藻能成为优势藻种的重要原因之一，也在水华的暴发过程中起到了调节作用。然而，人们至今尚未弄清气囊的结构及其合成降解机制。为了探究气囊合成相关蛋白的三维结构，进一步重构气囊这一中空结构的三维面貌，我们以铜绿微囊藻Microcystis aeruginosa PCC 7806中的气囊合成相关的一组Gvp蛋白为研究对象，利用X射线晶体学手段解析各个气囊蛋白的结构，并联合运用高分辨率冷冻电镜，蛋白质免疫印迹法和胶体金标记等方法来分析各结构蛋白的具体定位。该项目将解析气囊原子分辨率水平上的三维结构，对治理水华暴发有一定理论指导意义。	Microcystis aeruginosa was investigated and identified as a planktonic unicellular cyanobacterium which is responsible for algal bloom in the freshwater environments. In Microcystis cells, an abundant production of intracellular structures, the gas vesicle, an inert, hollow and gas-filled structure, formed solely from proteins, provides cells with buoyancy and regulates their vertical distribution in natural waters. Cyanobacteria could float taxis toward air-liquid interfaces of water environments, positioning themselves at a depth with optimal light and oxygen supply for better growth, subsequent niche colonization and water-bloom formation. However, the fine structure of gas vesicle and its  biosynthesis/degradation mechanisms are still unclear. To determine three dimensional structures of gas vesicle proteins and remodeling the integral hollow structure, we are committed to solve structures of Gvp proteins from Microcystis aeruginosa PCC 7806 using X-ray crystallography. Moreover, in combination with high-resolution cryo-electron microscopy, we will investigate the localization of individual Gvp proteins by immunoblotting and immunogold labeling-based tomography. These findings will provide insights into structural characteristics of gas vesicle and the rational control of algal bloom.	博士后
-	膜环境对膜蛋白DAGK结构与功能的影响	31500603	青年科学基金项目	中国科学院武汉物理与数学研究所	陈艳可	20	2015	膜蛋白结构；固体核磁共振；天然膜；去垢剂；甘油二脂激酶	是	3;0;0;0;0	201322	100150871	630	C050101	2016-01至2018-12	膜蛋白的结构与功能深受所处环境的影响。目前，在PDB数据库中收录的膜蛋白结构90%以上是在膜模拟环境—去垢剂胶束中解析的。然而，在去垢剂的环境中，膜蛋白的真实结构能否被维持是备受结构生物学家关注的问题。大肠杆菌甘油二脂激酶(DAGK)是一个很重要的三跨膜蛋白，其三维结构已经被液体核磁共振和X-Ray晶体衍射的方法在去垢剂胶束或脂质立方相中所解析，然而由于环境的不同，得到的结构差别很大，并且这两种结构都不是在DAGK的天然膜环境中进行解析的。固体核磁共振技术可以在接近膜蛋白天然环境的磷脂双层膜中解析其三维结构，是测定与证实膜蛋白结构的有力工具。本项目拟采用固体核磁共振技术在大肠杆菌磷脂膜的环境下对DAGK的三维结构进行解析，并分析不同环境下DAGK活性区域的结构变化，阐释膜蛋白结构与功能对膜环境的依赖性。	The structures of membrane proteins are profoundly influenced by membrane–protein interactions. To date, more than 90% structures of membrane protein in the PDB have been determined in membrane mimetic environments-detergent micelles. However, it is very difficult to obtain membrane mimetic environments that support the native structure and function of a membrane protein. Escherichia coli diacylglycerol kinase (DAGK) is a very important transmembrane protein of which three dimensional structure has been determined in detergent micelles or lipid cubic phase by solution-state NMR or X-Ray crystallography. Due to the different membrane mimetic environments, the two structures differ obviously. Solid-state NMR is a powerful tool for studying structures of membrane proteins in the native-like membrane environments. This project aims to use Solid-state NMR to determin the sturcture of DAGK in Escherichia coli total lipids bilayer. Then, we will expain the influence of membrane environments on membrane protein structure and function by comparation the structures of DAGK active domain in different membrane environments.	助理研究员
-	与ALS/FTD相关联的C9orf72六核苷酸重复扩增形成G-四链体的结构研究	31500604	青年科学基金项目	香港科技大学深圳研究院	周波	20	2015	核磁共振；G-四链体；C9orf72六核苷酸重复扩增；肌萎缩性侧索硬化症；额颞叶痴呆	是	2;0;0;0;0	404024	100175543	630	C050101	2016-01至2018-12	肌萎缩性侧索硬化症（ALS）和额颞叶痴呆（FTD）是严重的神经退行性疾病。在家族性或散发性ALS/FTD患者中，位于9号染色体第72个开放阅读框基因（C9orf72）的GGGGCC六核苷酸重复扩增（HRE）是最常见的遗传致病因子。以往研究表明，C9orf72 HRE无论是作为DNA或转录的RNA产物，均可折叠成具有不同结构的G-四链体，并与ALS/FTD的致病机理密切相关。由于缺乏相关G-四链体的高分辨率结构信息，C9orf72 HRE形成G-四链体的分子机理仍不清楚。本研究将利用核磁共振技术首次获取C9orf72 HRE DNA及RNA G-四链体的高分辨率结构，对于在ALS/FTD患者中由于此种结构导致的异常转录产物诱发疾病的分子机理提供极有价值的信息，并且为针对C9orf72 HRE G-四链体设计小分子用以靶向调节ALS/ FTD的发病机制奠定必要的结构学基础。	Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are devastating neurological diseases. Abnormal expansion of a hexanucleotide repeat, (GGGGCC)n, is the most common genetic cause of familial and sporadic forms of ALS and FTD. This nucleotide repeat element is located in a non-protein-coding region of the C9orf72 gene. Previous studies suggested that the C9orf72 hexanucleotide repeat expansion (HRE), either as DNA or the transcribed RNA, can fold into G-quadruplexes with distinct structures. It could also form transcriptionally induced RNA-DNA hybrids known as R-loops. These structural polymorphisms lead to C9orf72 HRE-containing abortive transcripts, which may aggregate and form RNA foci in patient cells. Despite the critical connection of C9orf72 HRE G-quadruplexes to the pathogenic mechanism of C9orf72 HRE-linked ALS/FTD, the molecular basis of G-quadruplex formation by C9orf72 HRE remains elusive..In this project, we plan to perform systematic biochemical and structural characterizations for C9orf72 HRE G-quadruplexes. First, we will determine the 3D structure of G-quadruplex formed by the C9orf72 HRE DNA. In our preliminary study, we successfully obtained a homogenous DNA sample, d(GGGGCC)4, which favored a monomeric G-quadruplex fold. We have determined the topology of this G-quadruplex DNA using the nuclear magnetic resonance (NMR) approach. It forms a chair-type G-quadruplex with a four-layer antiparallel G-tetra core and three edgewise loops, which is distinct from known structures of chair-type G-quadruplexes. We will further resolve its detailed structure using NMR techniques. We have also successfully obtained a homogeneous C9orf72 HRE RNA sample with sufficient quality for NMR structure determination. Unlike the monomeric d(GGGGCC)4 DNA, this RNA, r(GGGGCC)GGGG, is an asymmetric dimer. We will perform more NMR studies to obtain its 3D structure. As no structure of the C9orf72 HRE G-quadruplex has ever been solved, the structural information of C9orf72 HRE DNA/RNA G-quadruplexes to be obtained in the current project will provide valuable insights into the molecular mechanism of abortive transcripts formation by C9orf72 HRE and RNA foci appearance in ALS/FTD patients. The outcome of the proposed research will not only provide insight into the molecular mechanism underlying the C9orf72 HRE G-quadruplex formation in the etiology of ALS/FTD, but may also lay the necessary basis for designing small molecules that therapeutically target C9orf72 HRE G-quadruplexes for the modulation of ALS/FTD pathogenesis.	副研究员
-	Sema-Plexin信号通路中FARP2的结构与功能研究	31500605	青年科学基金项目	华中科技大学	贺晓静	21	2015	蛋白质结构；相互作用；轴突导向	是	2;0;0;0;0	100113	100154722	630	C050101	2016-01至2018-12	神经系统的精确发育发展离不开轴突导向。神经细胞生长椎上的受体接受环境中的轴突导向因子传递的信号，经过一系列蛋白的传递，最后作用于细胞骨架蛋白，从而影响生长椎的走向。Semaphorin-Plexin 通路是其中重要的信号通路之一，我们的研究重点是这一通路中plexin的下游互作蛋白FARP2。FARP2 N端的FERM结构域介导它与Plexin之间的相互作用，但是二者之间的互作模式与分子机制还不清楚。本项目将利用晶体生物学，生物化学，细胞生物学等手段，在结构与功能上研究FARP2及其与Plexin的互作关系和分子调控机制，为进一步理解Sema-Plexin通路下游信号传导机制提供分子依据。我们之前的结构生物学研究发现FARP2 的DH-PH-PH结构域是一种以自我抑制构象存在的小GTP酶的鸟核苷酸交换因子(GEF)，本项目将进一步探讨如何激活FARP2的GEF活性。	英文摘要.The correct wiring of the nervous system relies on the precise axon guidance. During development of the nervous system, axons are guided to their proper targets by sensing a variety of extracellular cues in the local environment. The receptor protein on the neuronal growth cones which is located at the tip of the growing axon, recognizes guidance cues. The signal finally selectively alters the stability of the actin cytoskeleton and microtubules that determine the rate and direction  of   axon  extension.  Semaphorin-Plexin  is  one  of  the  classic ligand/receptor systems involved in this process， and we will focus on FARP2, which is a downstream partner of Plexin A1. FARP2 interacts with Plexin A1 though its N terminal FERM domain, but how they bind is still not clear. We are using  the  combination  of  protein  X-ray  crystallography,  biochemical techniques and cell based assay to study the structure and function of FARP2 and its interaction and regulation with Plexin A1. Our research will help us to understand the molecular regulation mechanisms of downstream signal transduction of Sema-plexin pathway.  C terminal domain DH-PH-PH of FARP2 is an auto-inhibited Guanine nucleotide exchange factor (GEF) based on our previous studies, and we will study how to active GEF activity further.	教授
-	Tip49a/Tip49b及其相关复合物的冷冻电镜结构研究	31500606	青年科学基金项目	德州学院	宋峰	20	2015	冷冻电镜；单颗粒三维重构；蛋白复合物组装	是	4;0;0;0;0	400969	100181269	630	C050101	2016-01至2018-12	Tip49a和Tip49b是AAA+超家族的两个蛋白，它们保守地存在于从酵母到人的多个物种中，在细胞内通常以复合物的形式存在。它们在DNA损伤修复、转录调控、snoRNP成熟、染色质重塑等生命活动中发挥重要的调控作用，但迄今为止仍然没有Tip49a/Tip49b全长蛋白相关复合物的结构报道。本研究拟主要应用冷冻电镜单颗粒三维重构技术解析人源Tip49a/Tip49b及其参与形成的两种高级复合物（R2TP、Tip49a/Tip49b-核小体）的高精度三维结构，并结合生化实验确定Tip49a/Tip49b在两种高级复合物中的作用。本项目的研究成果将为理解Tip49a/Tip49b在snoRNP组装（R2TP复合物）和ATP依赖的染色质重塑（Tip49a/Tip49b-核小体复合物）中的工作机制提供可靠的结构信息。	Tip49a and Tip49b are two structurally and functionally highly related proteins that belong to the AAA+ (ATPase Associated with diverse cellular Activities) superfamily. They are existed in many species of which ranging from yeast to human. Both Tip49a and Tip49b are conserved components of various multi-subunit complexes, which are linked to a wide range of cellular processes, such as DNA damage response, transcription regulation, snoRNP biogenesis and ATP-dependent chromatin remodeling. Despite their diverse roles, there is no available high resolution structure of full-length Tip49a/Tip49b protein complex. The mainly purpose of our research is to reveal the high resolution structures of dodecameric Tip49a/Tip49b and determine their functions in two larger complexes which containing them, R2TP and Tip49a/Tip49b-nucleosome complex, by using cryo-EM single particle analysis combining with biochemical and biophysical techniques. Our research will provide insights into the structural basis of Tip49a/Tip49b in mediating snoRNP biogenesis(R2TP complex) and ATP-dependent chromatin remodeling(Tip49a/Tip49b-nucleosome complex).	教授
-	结核分枝杆菌分枝菌酸合成途径脱水酶HadABC复合物与多种抗结核抑制剂的结构和功能研究	31500607	青年科学基金项目	中国科学院上海生命科学研究院	李俊	20	2015	结核分枝杆菌；晶体结构；分枝菌酸；脱水酶；药物靶点	是	3;0;0;0;0	201022	100175031	630	C050101	2016-01至2018-12	结核病是目前世界上致死率最高、传播范围最广的细菌性疾病。结核分枝杆菌是引发结核病的病原菌，由于耐多药菌株（MDR-TB）和广泛耐药菌株（XDR-TB）的出现，使得现有药物的治疗几乎失效。因此，寻找新的药物靶点以及研究全新作用机制的强力抗结核药物已经成为迫在眉睫的重要任务。由致密的分枝菌酸层构成的细胞壁使得结核分枝杆菌可以逃避免疫攻击和有害物质入侵从而能够存活。脱氢酶HadAB和HadBC是II型分枝菌酸脂链延伸系统（FAS-II）中最晚被发现的两对复合物，也是一线药物异烟肼靶点InhA的下游蛋白。迄今为止，其三维结构和催化机制尚不清楚。本研究项目可以填补这方面的空白，从分子水平上推进其酶活机制的研究；而HadABC与黄酮类抑制剂和抗结核药物Isoxyl、Thiacetazone复合物结构研究将揭示其抗结核的抑制机制，对基于HadABC的抗结核药物开发提供重要线索和可靠的结构生物学基础。	Tuberculosis (TB) is the most lethal and widely spread bacterial infectious disease over the world, mainly caused by the pathogenic Mycobacterium tuberculosis (Mtb). Seriously, the emergence of Multi-drug resistant TB (MDR-TB) and extensively drug resistant TB (XDR-TB) make currently used drugs ineffective to cure TB. Therefore, developing novel and effective anti-TB drugs following research of newly found drug targets has already been an urgent and important mission now. Mtb is hard to kill under host immune attack and survives from toxicant invasion because of the dense and hydrophobic mycolic acid layer of cell wall. Both of HadAB and HadBC were the dehydratases, which were the last and latest identified piece of the type II fatty acid synthesis (FAS-II) system, involved in the elongation of mycolic acid chain. The importance of mycolic acid for Mtb makes all the enzymes in this synthesis pathway potential drug targets including HadAB and HadBC. In fact, they were exact downstream enzymes of InhA, an approved target of currently first-line drug isoniazid. So far as we know, there are no crystal structures of HadAB and HadBC reported and the knowledge of catalytic mechanism is unclear as well. Thus, our research will fill in these gaps by deepening our understanding of it enzymatic catalysis from molecular perspective. Our research also aims to unveil inhibition mechanisms by studying the complex structures of HadABC with either flavonoid inhibitors or anti-TB drugs Isoxyl and Thiacetazone, which will lay sound structural basis and provide important clues for the anti-TB drug development.	副研究员
-	单颗粒低温透射电镜高分辨率数据收集用支持膜的研究	31500608	青年科学基金项目	中国科学院生物物理研究所	黄小俊	20	2015	冷冻电镜成像技术；单颗粒三维重构；单颗粒冷冻电镜法	是	0;0;0;0;2	100067	100172851	630	C050101	2016-01至2018-12	单颗粒低温透射电镜技术发展至今，最大的瓶颈在于样品制备。而样品制备不可或缺的耗材是透射电镜载网。透射电镜载网（特别是覆在其上的支持膜）的亲水性能，机械性能，导电性能等直接影响着制备样品的质量及数据收集效率。本项目在已自主研制并应用的GIG微阵列碳支持膜的基础上，继续研发更符合实际需要的特定厚度、孔径及孔间距的微阵列支持膜，并以提升支持膜的导电性为目标以开发出第二代的该系列微阵列支持膜。最终将第二代的微阵列支持膜应用到低温透射电镜技术中，降低电子束引发的图像漂移状况，提升单颗粒低温透射电镜成像质量和数据收集效率。	Single particle cryo electron microscopy develops very fast these years. The bottle neck of this technique is at sample preparation. Among all those important factors of sample preparation, e.g. protein purity, concentration, rigidity et al., the properties of TEM grid, to be specific, the properties of supporting film on the TEM grid, is essential to preparing a good cryo sample. Hydrophilicity, strong mechanical strength, high conductivity of the supporting film affect the quality of prepared cryo sample and the efficiency of data collection. Based on the self-developed amorphous carbon film with fixed-pattern micro array (brand name GIG), this study aims to develop more suitable supporting films for cryoTEM usage. It includes designing suitable film thickness, hole size, spacing between hole which leads to high efficiency data collection, and increasing the conductivity of the supporting film at liquid nitrogen temperature which reduces the beam induce movement and enhances the quality of cryoEM images.	高级工程师
-	干扰素诱导蛋白IFIT/ISG56家族抗病毒功能的结构生物学研究	31500609	青年科学基金项目	中国科学院生物物理研究所	冯峰	20	2015	IFIT/ISG56家族蛋白；抗病毒；天然免疫	是	1;0;0;0;0	100067	100218232	630	C050101	2016-01至2018-12	病原体和干扰素能够诱导ISG56/IFIT 家族蛋白的表达, 它们不仅具有抗病毒作用，而且还参与调节细胞的免疫反应。前期我们在国际上率先解析了该家族成员的晶体结构，并且通过结构信息证实了其抗病毒功能与核酸结合能力有关，但是其背后的分子机制尚不明确。本项目拟通过结构生物学结合细胞生物学的手段，在已获得的研究结果基础上系统地开展ISG56/IFIT 家族各个成员的抗病毒和免疫功能的分子机制的研究，包括比较家族成员之间的晶体结构差异；明确识别和结合核酸的序列和结构的特异性；检测在免疫反应信号通路中相互作用的分子，最终揭示家族各成员选择性激活表达的条件和特异性抗病毒的原因。本项目的研究成果将对宿主抗病毒天然免疫领域的研究以及相应的免疫临床治疗具有重要的理论和现实意义。	ISG56/IFIT family proteins，which be induced by interferon and pathogen，have antiviral functions and can regulate cellular immune response. Previously, we first solved the crystal structure of ISG56/IFIT family proteins and discovered that their antiviral functions are related to their ability to recognize nucleotides. However, the molecular mechanism remains unknown. In this project, we aim to reveal the mechanism of ISG56/IFIT proteins using structural and cellular biology methods. Base on the information on crystal structure differences, nucleic acid recognitions, binding partners in innate immune pathway, we try to propose the mechanism of specificity of ISG56/IFIT family proteins' antiviral functions. Our results will deepen people's understanding on innate immune response and provide practical significance on clinical treatment.	博士后
-	Wnt信号通路中β-catenin及其细胞核内共激活因子复合物的结构生物学研究	31500610	青年科学基金项目	中国科学院生物物理研究所	孙伟	20	2015	蛋白质；相互作用；晶体筛选；结构解析；分子置换	是	1;0;0;0;0	100067	100045287	630	C050101	2016-01至2018-12	Wnt/β-catenin信号通路的过度激活会导致许多癌症的发生。β-catenin是该通路上的中心效应分子，它的表达上调是这些癌症发生的驱动因素。在细胞核内，多种共激活因子与β-catenin相互作用，共同激活下游肿瘤促进因子如cyclin-D和c-Myc的转录，其中M1型叉头框蛋白（FoxM1）和PCNA相关因子（PAF）就是其中两个。FoxM1促进β-catenin在细胞核内的定位，并可以促进Wnt应激基因的表达，在人类的多种肿瘤（比如神经胶质瘤）中都有过表达。PAF则在结直肠癌和肠干细胞中特异表达。因为β-catenin-FoxM1和β-catenin-PAF复合体的形成是Wnt/β-catenin下游的重要事件，对肿瘤的发生及恶化起重要作用，我们计划对它们开展结构生物学研究，以便阐释相关癌症的发生机理，并为人类癌症治疗提供新的思路。	Hyperactivation of the canonical Wnt/β-catenin signaling pathway can cause many types of cancers. β-catenin is the central effector of this signaling pathway, and its upregulation is a driving factor for these cancers. In the nucleus, many coactivators interact with β-catenin, activating transcription of downstream tumor-promoting factors such as cyclin-D and c-Myc. Forhead box protein M1 type (FoxM1) and PCNA-associated factor (PAF) are two β-catenin-specific transcriptional coactivators. FoxM1 promotes β-catenin nuclear localization and induces expression of Wnt responsive genes, and is overexpressed in many cancer types, including glioma. As to PAF, it is specifically expressed in colon cancer and intestine stem cells.  Because formations of β-catenin-FoxM1 and β-catenin-PAF complex are critical events downstream of Wnt/β-catenin signaling pathway, which play vital roles in tumorigenesis and metastasis of many cancers, we embark on investigating the interactions between β-catenin and FoxM1/PAF employing structural biological methods.  We aim to elucidate the molecular mechanism of tumorigenicity and try to provide novel insights into the therapy of human cancers.	博士后
-	应用电子顺磁共振技术探究结核分枝杆菌分泌系统内膜蛋白Rv3882c跨膜结构域的结构特征	31500611	青年科学基金项目	中国科学院合肥物质科学研究院	于璐	20	2015	分枝杆菌分泌系统；膜蛋白；位点特异性自旋标记；电子顺磁共振；结构测定	是	2;0;0;0;0	100212	100134186	630	C050101	2016-01至2018-12	结核分枝杆菌的ESX-1分泌系统能使菌体分泌的致病因子、存活因子等蛋白质穿过其高度疏水致密的细胞被膜，对结核分枝杆菌的毒力和存活极为关键。因此，有关ESX-1分泌系统相关组成蛋白的结构分析对于理解结核杆菌感染机制具有非常重要的意义。Rv3882c蛋白是ESX-1分泌系统中一种重要的内膜蛋白，可能与其他组成蛋白共同形成通道类复合物，负责转运底物穿过细胞被膜，但目前其空间结构和确切的生物学功能尚不明确，仍亟待研究。本项目将结合位点特异性自旋标记与电子顺磁共振技术，通过获取Rv3882c蛋白跨膜结构域的运动性信息、易趋性信息以及在膜环境中的取向信息，综合分析得到Rv3882c蛋白跨膜结构域在膜环境中的三维结构模型。本项目的顺利开展，将为Rv3882c蛋白的结构研究提供重要依据，有助于进一步阐明结核分枝杆菌的分泌系统与致病机制，也为应用电子顺磁共振技术研究其他膜蛋白结构提供方法与思路。	The ESX-1 secretion system of Mycobacterium tuberculosis serves to secrete proteins, such as virulence factors and survival factors, across its highly hydrophobic and poorly permeable cell envelop, which is crucial for the virulence and survival of Mycobacterium tuberculosis. Therefore, structural investigation on component proteins of ESX-1 secretion system is very important for understanding the infection mechanisms of Mycobacterium tuberculosis. Rv0082c is a very important membrane protein of ESX-1 secretion system and is located on the inner membrane of Mycobacterium tuberculosis. It was predicted that Rv3382c forms a channel-like complex with other proteins and functions to transport the substrates across the mycobacterial cell envelope. However, the structure and function of this protein is still unclear. In this proposal, we are trying to characterize the structure of the transmembrane domain of membrane protein Rv3882c by combing Site Directed Spin Labelling (SDSL) technology and Electron Paramagnetic Resonance (EPR) spectroscopy. The acquired mobility, accessibility and orientation information in membrane will be integrated to derive a three dimensional structural model of the transmembrane domain of Rv3882c. Successful implementation of this project will not only yield valuable information for structural determination of Rv3882c, but also provide deeper insights of the protein secretion system and pathogenic mechanism of Mycobacterium tuberculosis. Also, this project will provide method of using EPR as the tool for structural studies of other membrane proteins.	副研究员
-	真核生物mRNA转录出核复合物TREX-1的结构与功能研究	31500612	青年科学基金项目	许昌学院	苏测洋	20	2015	mRNA转录出核复合物；THO复合物；蛋白质结构生物学；X-射线晶体学；冷冻电镜	是	0;0;0;0;0	400411	100181698	630	C050101	2016-01至2018-12	真核生物mRNA转录出核复合物TREX-1广泛存在于从酵母到哺乳动物中，参与mRNA的转录、转录后加工和出核运输等一系列过程。有报道指出，TREX-1复合物组分在很多癌症组织中检测到表达异常。TREX-1复合物在真核生物中保守性较高，酵母源TREX-1复合物由Sub2、Yra1和THO复合物组成，人源TREX-1复合物由Uap56、Yra1以及人源THO复合物组成。目前，缺乏TREX-1复合物的高分辨率三维结构，这极大的阻碍了对其参与pre-mRNA加工分子机理的深入研究。我们之前的研究通过昆虫杆状病毒体外重组表达获得了高纯度的酵母源THO复合物。在此基础上，本项目拟对酵母和人源的TREX-1复合物进行组装与纯化，通过结合蛋白质X射线晶体学和冷冻电镜技术，以期获得TREX-1复合物高分辨率三维结构，并辅以生物化学和细胞生物学技术，研究其组装及参与mRNA出核的分子机制。	Eukaryotic mRNA TRanscription/EXport complex-1 (TREX-1 complex) is evolutionarily conserved multi-protein complex from yeast to human, participating in mRNA transcription, post-transcription processing and export. Previous report indicated that different protein component of TREX-1 complex has dysregulated expressed in different cancer specimens. Yeast TREX-1 complex consists Sub2, Yra1 and THO complex, while human TREX-1 complex consists Uap56 (yeast Sub2 homologous protein), Aly (yeast Yra1 homologous protein) and human THO complex. The detail mechanism of how TREX-1 complex participate pre-mRNA maturation and export is still obscurity, due to the miss of high-resolution 3D structural model of TREX-1 complex. In previous study, we get highly purified yeast THO complex through recombinant baculovirus expression system. Based on these, we try to reconstitute yeast and human TREX-1 complex in vivo and in vitro, through protein X-ray crystallography and cyro-EM technology, aim to get high-resolution 3D structure of TREX-1 complex. We also try to use biochemical and cell biology method to investigate the molecular mechanism of TREX-1 assembling and its participation mRNA export.	讲师
-	一种新的葡萄糖脱氢酶FAD-GDH的晶体结构与催化机制研究	31560244	地区科学基金项目	遵义医科大学	杨愈丰	40	2015		否	0;0;0;0;0			631	C050101	2016-01至2019-12			
-	高等植物PSII-LHCII超复合物的三维结构研究	31570724	面上项目	中国科学院生物物理研究所	曹鹏	70	2015		否	0;0;0;0;0			218	C050101	2016-01至2019-12			
-	铁吸收调控蛋白Fur的复合物结构和识别机制研究	31570725	面上项目	中国农业大学	陈忠周	65	2015		否	0;0;0;0;0			218	C050101	2016-01至2019-12			
-	中介体核心复合物调控RNA聚合酶II的结构机制研究	31570726	面上项目	中国科学技术大学	王雪娟	60	2015		否	0;0;0;0;0			218	C050101	2016-01至2019-12			
-	基于冷冻电镜的呼肠孤病毒转录的分子机制研究	31570727	面上项目	清华大学	程凌鹏	62	2015		否	0;0;0;0;0			218	C050101	2016-01至2019-12			
-	肺炎链球菌荚膜多糖合成途径的结构酶学	31570728	面上项目	中国科学技术大学	周丛照	62	2015		否	0;0;0;0;0			218	C050101	2016-01至2019-12			
-	核小体水平上组蛋白修饰酶和组蛋白密码识别因子参与表观遗传调控的分子机理研究	31570729	面上项目	北京师范大学	王占新	65	2015		否	0;0;0;0;0			218	C050101	2016-01至2019-12			
-	冷冻电镜数据采集和实时电子显微图像处理技术研究	31570730	面上项目	清华大学	李雪明	70	2015		否	0;0;0;0;0			218	C050101	2016-01至2019-12			
-	核小体组蛋白H4被picNuA4复合物选择性乙酰化的结构基础	31570731	面上项目	清华大学	陈柱成	62	2015		否	0;0;0;0;0			218	C050101	2016-01至2019-12			
-	小分子热休克蛋白的结构与作用机制	31570732	面上项目	北京大学	尹长城	65	2015		否	0;0;0;0;0			218	C050101	2016-01至2019-12			
-	ABC转运蛋白的结构与功能研究	31570733	面上项目	清华大学	杨茂君	65	2015		否	0;0;0;0;0			218	C050101	2016-01至2019-12			
-	细菌外源基因抑制因子的结构与功能研究	31570734	面上项目	北京大学	夏斌	70	2015		否	0;0;0;0;0			218	C050101	2016-01至2019-12			
-	分泌系统内新型激酶的结构和底物识别机制研究	31570735	面上项目	北京大学	肖俊宇	62	2015		否	0;0;0;0;0			218	C050101	2016-01至2019-12			
-	衣原体III型分泌系统结构的低温电镜研究	31570736	面上项目	中山大学	张勤奋	60	2015		否	0;0;0;0;0			218	C050101	2016-01至2019-12			
-	人的SMN复合物识别snRNA调控snRNP装配的结构生物学研究	31570737	面上项目	中国科学技术大学	许超	62	2015		否	0;0;0;0;0			218	C050101	2016-01至2019-12			
-	光合玫瑰菌核心光合复合体的结构与功能研究	31570738	面上项目	杭州师范大学	徐晓玲	62	2015		否	0;0;0;0;0			218	C050101	2016-01至2019-12			
-	神经肽Y受体NPY1R的结构生物学研究	31570739	面上项目	中国科学院上海药物研究所	吴蓓丽	70	2015		否	0;0;0;0;0			218	C050101	2016-01至2019-12			
-	具有新颖催化活性的细胞色素P450酶TxtE和甲基转移酶TleD的晶体结构和功能研究	31570740	面上项目	中国科学院上海应用物理研究所	郁峰	62	2015		否	0;0;0;0;0			218	C050101	2016-01至2019-12			
-	Liprin-α介导的神经突触形成中活性区组装机制的研究	31570741	面上项目	南方科技大学	魏志毅	62	2015		否	0;0;0;0;0			218	C050101	2016-01至2019-12			
-	基于冷冻电镜二十面体对称失配三维重构的腺病毒结构研究	31570742	面上项目	湖南师范大学	刘红荣	62	2015		否	0;0;0;0;0			218	C050101	2016-01至2019-12			
-	糖原代谢关键蛋白质的结构和功能研究	31570743	面上项目	中国科学院上海生命科学研究院	向嵩	60	2015		否	0;0;0;0;0			218	C050101	2016-01至2019-12			
-	蛋白质晶体学结构测定新技术研究	31570744	面上项目	中国科学院高能物理研究所	董宇辉	65	2015		否	0;0;0;0;0			218	C050101	2016-01至2019-12			
-	内吞性胶原蛋白受体Endo180 的结构研究	31570745	面上项目	福州大学	袁彩	62	2015		否	0;0;0;0;0			218	C050101	2016-01至2019-12			
-	线粒体解偶联蛋白UCP1的结构和功能解析	31570746	面上项目	中国科学院上海生命科学研究院	周界文	65	2015		否	0;0;0;0;0			218	C050101	2016-01至2019-12			
-	参与基因表达转录后调控的重要蛋白质-RNA复合物的结构与功能研究	31570747	面上项目	中国科学院生物物理研究所	刘超培	60	2015		否	0;0;0;0;0			218	C050101	2016-01至2019-12			
-	磷脂酰肌醇合成酶的结构与功能	31570748	面上项目	中国科学院上海生命科学研究院	李典范	62	2015		否	0;0;0;0;0			218	C050101	2016-01至2019-12			
-	负链RNA病毒聚合酶的结构和功能机制研究	31530015	重点项目	中国科学院生物物理研究所	刘迎芳	292	2015		否	0;0;0;0;0			220	C050101	2016-01至2020-12			
-	染色体的结构与功能研究	31525007	国家杰出青年科学基金	上海交通大学	雷鸣	350	2015		否	0;0;0;0;0			429	C050101	2016-01至2020-12			
+项目名称	批准号	项目类别	依托单位	项目负责人	资助经费(万元)	批准年度	关键词	是否结题	研究成果(期刊论文;会议论文;著作;奖励;专利)	依托单位ID	项目负责人ID	项目类别代码	申请代码	起止年月	中文摘要	英文摘要	负责人职称
+脱敏态GluA2配体结合域LBD二聚体系综结构及其调控的研究	31500595	青年科学基金项目	浙江大学	刘主	20	2015	谷氨酸受体；脱敏；顺磁核磁共振；小角X光散射；蛋白质系综结构	是	2;0;0;0;0	100152	100145756	630	C050101	2016-01至2018-12	研究蛋白质系综结构及分布比例使我们了解蛋白质如何行使功能。离子型谷氨酸受体2（GluA2）参与脑内重要的生理和病理过程。研究表明，GluA2为二聚—二聚组成的四聚体，其配体结合域（LBD）二聚体结构的变化对GluA2的配体门控至关重要。由于GluA2的LBD二聚作用极弱（KD值约为6mM），因此对其结构研究极少。最近我们实验发现，在脱敏条件下，LBD的瞬态二聚体存在多种构象。为解析脱敏态LBD二聚体原子分辨率的系综结构及分布比例，本项目拟采用化学交联质谱分析的方法获得低分辨率的系综构象和分布，同时运用顺磁弛豫增强的液体核磁共振技术解析原子分辨的系综结构，并联合小角X光散射以计算各构象比例。基于LBD二聚体的结构，我们将突变界面关键位点，结合电生理，阐明全长GluA2脱敏过程与脱敏态LBD二聚体系综结构的构效关系。据此，我们将从脱敏态LBD二聚体结构动态变化的角度揭示GluA2的脱敏机制。	Depiction of protein ensemble structure has allowed us to understand how the protein fulfills its function. Ionic glutamate acceptor 2 (GluA2) is involved in many important physiological and pathological processes in the brain. GluA2 is tetrameric (dimer of dimer), and its ligand binding domain (LBD) dimer plays a key role in the ligand gating of GluA2. As the LBD only weakly dimerizes by itself, there has been few studies on the ensemble structure of LBD dimer. We found that the LBD dimer adopts an array of relative orientations as the GluA2 shifts into the desensitized state. We thus propose to determine the ensemble structure of LBD dimer. We will use the CXMS (chemical cross-linking of proteins coupled with mass spectrometry analysis) analysis to obtain a low-resolution picture. Conjointly, we will use PRE (paramagnetic relaxation enhancement) NMR to further characterize the ensemble structure of LBD dimer, and use SAXS (small-angle x-ray scattering) to assess the relative populations of each conformational state. Based on the structural characterization, we will mutate key interfacial residues that may perturb the ensemble structure of LBD dimer, which will be confirmed by electrophysiological analyses. Together, we will illustrate how the structural change of LBD dimer accompanies the desensitization of GluA2. If funded and successfully carried out, the project will provide the structural basis for exquisite pharmacological modulation of GluA2 function.	教授
+帕金森病致病蛋白LRRK2的ROC结构域GTP水解抑制机制与结构生物学研究	31500596	青年科学基金项目	南京理工大学	廖静伶	20	2015	富亮氨酸重复激酶2；ROC结构域；GTP水解活性；结构功能学；帕金森病	是	2;0;0;0;0	100468	100118874	630	C050101	2016-01至2018-12	帕金森病是与年龄密切相关的神经退行性疾病之一。LRRK2基因是目前为止突变率最高的帕金森病致病基因，主要表现在LRRK2蛋白激酶活性的异常增高，但其具体生物功能及致病机制仍不明确。深入研究LRRK2蛋白正常生理功能及基因突变的致病机制将为研究帕金森病治疗策略提供分子机制水平的依据。LRRK2蛋白除了具有激酶活性以外，还拥有GTP水解酶活性，该GTP水解酶活性对激酶活性有调节作用，揭示LRRK2蛋白存在分子内调节机制。LRRK2蛋白特有的生化特征使其成为帕金森病非常有希望的治疗靶点。申请者将运用X射线蛋白晶体学，生物化学及生物物理学方法，通过解析LRRK2蛋白中的ROC结构域晶体结构及GTP水解抑制机制来阐明基因突变的致病机理，为新的通过调控GTP水解酶活性来降低LRRK2的激酶活性的方法提供理论依据。	Parkinson’s disease (PD) is a devastating neurological condition that ravages people’s quality of life as it progresses from the subtle loss of muscular coordination, to severe physical and mental disability, to eventual death. There is no cure and no available treatments to stop this disease progression. Today, mutations in LRRK2 are the most prevalent known genetic causes of Parkinson’s disease, for both familial and sporadic cases. In spite of the intensive efforts over the past decade, the molecular role of LRRK2 in disease pathogenesis, its function, and the effects of disease-causing mutations remain unknown. Understanding the underlying mechanism of LRRK2 normal function and how it is affected by the disease-associated mutations will reveal novel mechanism-based therapeutic strategies. In addition to LRRK2 being associated with PD and being the most promising drug target for the disease, LRRK2 is an immensely intriguing protein, in that it has two enzymatic activities (GTPase activity and Kinase activity) that, together with other non-enzymatic domains, potentially represent a unique example of an intramolecular signaling system. The concept of the Roc GTPase domain functioning as a molecular switch regulating the overall activity of LRRK2 is conceptually interesting from a biochemical perspective, and it is the key to LRRK2’s normal function and disease process. In addition to the relatively wide prevalence of LRRK2 in PD, it is the most attractive target for drug discovery, because over-activation of its kinase activity is linked to disease pathogenesis, and it is an enzyme with active sites well suited for binding potential drugs. Indeed, LRRK2 kinase activity was effectively inhibited by broad kinase inhibitors that compete for ATP in the ATP-binding pocket. However, their translation into the clinic has been difficult due to adverse effects. Various potential alternative strategies are being considered, including targeting the Roc domain. This proposed study seeks to define the structures of ROC domain and its mutants to understand the GTP hydrolysis mechanism and mutations pathogenesis by using X-ray diffraction crystallography, protein biochemistry and biophysics approaches, which could provide insight into locations on LRRK2 structures that are suitable for mechanism-based drug discovery.	副教授
+线性泛素链组装复合物(LUBAC)的调节机制研究	31500597	青年科学基金项目	中国科学院上海有机化学研究所	刘建平	20	2015	蛋白质复合物；X射线晶体衍射；泛素化；肿瘤坏死因子TNFα；细胞死亡	是	4;0;0;0;0	400014	100193226	630	C050101	2016-01至2018-12	线性泛素化是一类广泛参与炎症和先天免疫的新型泛素化修饰。迄今唯一的线性泛素链E3连接酶LUBAC复合物由调节亚基Sharpin、HOIL1和催化亚基HOIP组成。单独的HOIP处于自抑制状态，但可以被Sharpin或HOIL1激活。然而，HOIP的自抑制和激活、与Sharpin的相互作用机制仍然未知。Sharpin缺失小鼠表现出多器官炎症和TNFα通路异常。为了阐明LUBAC复合物的调控机制，本申请计划解析自抑制和激活状态的HOIP催化核心片段，以及Sharpin/HOIP复合物的结构，揭示HOIP的自抑制和激活机制，并设计点突变解除自抑制或者破坏Sharpin对HOIP的激活，研究相应突变体对细胞死亡或RIP1线性泛素化的影响，以检验我们的假说：Sharpin/HOIP复合物对RIP1的线性泛素化决定了TNFα通路的最终效应——炎症或细胞死亡。现有工作进展为实现上述目标奠定了坚实的基础。	Linear ubiquitination, a recently discovered novel type of ubiquitination, is extensively involved in numerous signaling pathways related to inflammation and innate immune. Linear ubiquitin chain assembly complex (LUBAC) is the sole identified E3 ubiquitin ligase that catalyzes the formation of linear poly-ubiquitin chain. It consists of two regulatory subunits Sharpin and HOIL1 as well as one catalytic subunit HOIP. The isolated HOIP is in an auto-inhibited state, but it can be activated by Sharpin or HOIL1 to sufficiently promote the linear ubiquitination of target substrates. However, the molecular mechanisms underlying the the auto-inhibition of HOIP, its activation by Sharpin or HOIL1, and the interaction between HOIP and Sharpin are largely unknown. Previous studies indicated that loss of Sharpin in the mouse caused immunodeficiency and multi-organ inflammation, and severely inhibited the linear ubiquitination of TNFα receptor signaling complex. Based on these findings, we propose a hypothesis: the linear ubiquitination level of RIP1 catalyzed by Sharpin/HOIP complex determines the outcome of TNFα signaling—inflammation or cell death. To further understand the regulatory mechanism of LUBAC complex, we aimed to solve the structures of the catalytic fragment of HOIP either in auto-inhibited or in activated states as well as the Sharpin/HOIP complex, thereby to uncover the auto-inhibition and activation mechanism of HOIP. Based on the solved structures, we will design point mutations to specifically disrupt the auto-inhibition or the trans-activation of HOIP mediated by Sharpin; we will further test our hypothesis by assessing the impact of these mutations on the linear ubiquitination level of RIP1 and the TNFα induced cell death. Our current research progress has laid the foundation for us to pursue the scientific goals in this proposal.	副研究员
+转录因子CcmR调控蓝细菌碳浓缩机制的结构生物学基础	31500598	青年科学基金项目	中国科学技术大学	成望	20	2015	蓝藻；碳浓缩机制；转录调控；晶体结构；异构效应	是	1;0;0;0;0	200654	100047316	630	C050101	2016-01至2018-12	蓝细菌是被广泛用于光合作用和碳浓缩机制(CO2-concentrating mechanism, CCM)研究的重要模式生物。CcmR是集胞藻PCC6803中的一个调控碳浓缩机制的全局性转录因子，在低碳信号下解除对CCM相关基因的抑制，引起表达上调，促进CO2的吸收，保证光合作用的顺利进行。我们将以CcmR apo-form四聚体晶体结构为基础，综合利用生物信息学、生物化学、分子生物学以及结构生物学手段，对CcmR与DNA和/或信号分子的相互作用及其二元和三元晶体结构进行系统研究，以期揭示CcmR的别构机理，并基于CcmR特异性识别的DNA序列鉴定其调控的下游基因网络。该项目将阐明CcmR的调控碳浓缩机制的结构基础，有望为生态平衡和农业生产提供理论指导。	Cyanobacterium is an ideal model for studying the photosynthesis and CO2-concentration mechanism (CCM). The transcriptional factor CcmR was first identified in the cyanobacterium Synechocystis sp. PCC6803. It serves as a global controller to increase the expression of CCM related genes, which are suppressed at a high Ci concentration, thus augmenting the uptake of CO2 for the efficacy photosynthesis. Based on our previously determined crystal structure of the apo-form CcmR tetramer, we will systematically investigate the interactions of CcmR with the putative allosteric molecule and its binding DNA, by combining the methodologies of bioinformatics, biochemistry, molecular biology and structural biology. The findings will enable us to elucidate the CcmR allosteric mechanism, and to identify the gene network under the control of CcmR. This project will provide insights into the CCM regulated by CcmR, and might be helpful for guiding the ecological balance control and agricultural production in the future.	博士后
+三维超分辨技术研究细胞核孔复合物的选择性屏障分布	31500599	青年科学基金项目	复旦大学	马炯	21	2015	细胞核孔复合物；FG屏障；单分子；超分辨显微镜；核孔传输	是	9;0;0;0;0	201361	100162892	630	C050101	2016-01至2018-12	细胞核孔复合物（NPC）是真核细胞中连接细胞质和细胞核之间的选择性双向通道。由富含苯丙氨酸-甘氨酸（FG）氨基酸片段的自然非折叠蛋白构成的FG-屏障,选择性地调控基因相关物质,按照被动运输或者主动介入运输的方式进出细胞核。然而，核孔内FG屏障间的相互作用以及分布状况仍然是极具争议的重要科学问题。本项目将基于申请人发明的单点斜入射激发快速超分辨显微镜技术，研究核孔传输蛋白或FG-蛋白片段与FG屏障反应的三维分布图像，从而获得FG-屏障在细胞核孔内完整的分布情况。另外,进一步检测核孔传输蛋白对FG屏障的分布影响，讨论核孔传输的自调控机制。还将从不同传输蛋白或FG-片段在传输过程中的竞争效果，讨论FG屏障对各类基因相关物质传输的优先顺序。最终，完整的三维FG屏障将对核孔蛋白缺失相关的白血病、阿尔兹海默症的致病机制，以及各种类病毒的侵入机制等核孔相关病理机制或基因治疗提供信息。	The nuclear pore complexes (NPCs) selectively mediate the bidirectional trafficking of macromolecules between the cytoplasm and the nucleus in eukaryotic cells. The selective barrier formed by natively unfolded phenylalanine-glycine (FG) nucleoporins (Nups) inside the NPC allows for passive and facilitated transport through the NPC. However, the interactions that form the FG-barrier and their spatial distribution in the NPC remain unresolved. Based on the single-point edge-excitation sub-diffusion (SPEED) microscopy techniques, the applicant's invention, three-dimensionally map the interaction distributions between the fluorescent transport receptors (TRs) or FG-fragment and FG barrier. Then, we obtain fully information of the FG-barrier distribution in the NPC. The conformation change of the FG-barrier by TRs would be discussed as self-regulating mechanism of nucleocytoplasmic transport. Also from the competitive effects during different FG-fragments and transport proteins during the transport discuss priorities for the various gene related transport. Finally，the complete three-dimensional FG-barrier distribution will provide information with leukemia, Alzheimer's disease pathogenesis, as well as various types of viruses invade mechanisms for NPC related pathological mechanism or gene therapy.	研究员
+成肌细胞融合蛋白myomaker的结构基础与作用机理	31500600	青年科学基金项目	清华大学	龚德顺	9	2015	膜蛋白；均一性；晶体筛选；结构解析；晶体结构	是	0;0;0;0;0	201260	100177698	630	C050101	2016-01至2016-12	Myomaker是新发现的一种可以直接调控成肌细胞融合和肌肉再生的蛋白，这是哺乳动物细胞中唯一一个被鉴定的肌肉特异性的调节蛋白。它促进成肌细胞融合以及肌肉再生的活性为受伤后的肌肉再生提供了新的机会，为肌肉性疾病的治疗提供了新的思路。然而，目前对其发挥功能的分子机理仍然一无所知。本项目拟从结构生物学的角度出发，解析其晶体结构，揭示其分子作用机理。	Myomaker, a new discovered myoblast fusion activator, which is the only identified muscle-specific protein that directly regulates myoblast fusion and muscle regeneration in mammals. These activities of myomaker provide new opportunities for muscle regeneration and new strategies for therapy of muscle diseases. However, the molecular mechanism of myomaker is still in the dark. The aim of this project is to determinate the crystal structure of myomaker and provide new insights into the functional mechanism of myomaker.	博士后
+布氏锥虫中参与基因转录调控的PAF1复合物的结构和功能研究	31500601	青年科学基金项目	中国科学技术大学	廖善晖	20	2015	PAF1复合物；转录调控；布氏锥虫；蛋白质结构；蛋白质相互作用	是	11;0;0;0;1	200654	100186764	630	C050101	2016-01至2018-12	真核生物基因转录的调控在时间和空间上都具有很高的复杂度，细胞内基因转录调节的异常与各类疾病密切相关。在研究转录调节的过程中，大量RNA聚合酶相关蛋白复合体被报道，其中PAF1复合物（RNA polymerase II associated factor complex, PAF1C）就是最近发现的一种。PAF1复合物含有至少 5个不同的蛋白亚基，能够协同其他的转录因子及组蛋白修饰酶来调控转录过程。锥虫是一类单细胞真核原生生物，能够引起多种锥虫病。目前在布氏锥虫属中发现的PAF1复合体组成与高等真核生物不完全保守，可能暗示了布氏锥虫特有的基因转录调节方式。本项研究将结合结构生物学和细胞生物学方法，研究布氏锥虫中PAF1复合物的结构及其在基因转录调控中的作用。本研究不仅将丰富我们对布氏锥虫PAF1复合物和基因转录调控的认识，对于我们了解真核生物PAF1复合物和基因转录调控的进化也具有重要意义。	Eukaryotic gene transcription regulation is extremely complex in space and time. Any defect of transcription process is closely related to a variety of diseases. Many protein complexes have been reported during the study of transcription regulation, PAF1C (RNA polymerase II associated factor 1 complex) is such a complex discovered recently. PAF1C, contains at least 5 subunits. It participates in gene transcription regulation cooperatively with other transcription factors and histone modification enzymes. Trypanosomatids, the causative pathogens of trypanosomiasis, are a group of unicellular protozoa. The compositions of PAF1C of Trypanosoma brucei (T. brucei) is not fully conserved with that from higher eukaryotes, which may imply species-specific regulation pathway of gene transcription. Here, we are trying to explore the structure of PAF1C and its role in gene transcription regulation in T. brucei, by combining the techniques of structural biology and cell biology. This study will not only enrich our knowledge of PAF1C’s role in transcription regulation in T. brucei, but also has important implications for our understanding of the evolution of eukaryotic PAF1 complex and gene transcription regulation.	副研究员
+铜绿微囊藻气囊蛋白的结构和功能研究	31500602	青年科学基金项目	中国科学技术大学	代亚男	20	2015	铜绿微囊藻；气囊；气囊蛋白；晶体结构；结构蛋白	是	0;0;0;0;0	200654	100047317	630	C050101	2016-01至2018-12	铜绿微囊藻是一种单细胞浮游蓝藻，能大量产生气囊，营养丰富时在淡水水体表面聚集暴发水华。气囊是一种完全由蛋白质组成的中空、充满气体的惰性结构。气囊为藻细胞提供浮力，使其自行调节在自然水体中的垂直位置，漂浮到氧气和光照都适宜的位置以利于自身生长和生境殖民化。气囊不仅是铜绿微囊藻能成为优势藻种的重要原因之一，也在水华的暴发过程中起到了调节作用。然而，人们至今尚未弄清气囊的结构及其合成降解机制。为了探究气囊合成相关蛋白的三维结构，进一步重构气囊这一中空结构的三维面貌，我们以铜绿微囊藻Microcystis aeruginosa PCC 7806中的气囊合成相关的一组Gvp蛋白为研究对象，利用X射线晶体学手段解析各个气囊蛋白的结构，并联合运用高分辨率冷冻电镜，蛋白质免疫印迹法和胶体金标记等方法来分析各结构蛋白的具体定位。该项目将解析气囊原子分辨率水平上的三维结构，对治理水华暴发有一定理论指导意义。	Microcystis aeruginosa was investigated and identified as a planktonic unicellular cyanobacterium which is responsible for algal bloom in the freshwater environments. In Microcystis cells, an abundant production of intracellular structures, the gas vesicle, an inert, hollow and gas-filled structure, formed solely from proteins, provides cells with buoyancy and regulates their vertical distribution in natural waters. Cyanobacteria could float taxis toward air-liquid interfaces of water environments, positioning themselves at a depth with optimal light and oxygen supply for better growth, subsequent niche colonization and water-bloom formation. However, the fine structure of gas vesicle and its  biosynthesis/degradation mechanisms are still unclear. To determine three dimensional structures of gas vesicle proteins and remodeling the integral hollow structure, we are committed to solve structures of Gvp proteins from Microcystis aeruginosa PCC 7806 using X-ray crystallography. Moreover, in combination with high-resolution cryo-electron microscopy, we will investigate the localization of individual Gvp proteins by immunoblotting and immunogold labeling-based tomography. These findings will provide insights into structural characteristics of gas vesicle and the rational control of algal bloom.	博士后
+膜环境对膜蛋白DAGK结构与功能的影响	31500603	青年科学基金项目	中国科学院武汉物理与数学研究所	陈艳可	20	2015	膜蛋白结构；固体核磁共振；天然膜；去垢剂；甘油二脂激酶	是	3;0;0;0;0	201322	100150871	630	C050101	2016-01至2018-12	膜蛋白的结构与功能深受所处环境的影响。目前，在PDB数据库中收录的膜蛋白结构90%以上是在膜模拟环境—去垢剂胶束中解析的。然而，在去垢剂的环境中，膜蛋白的真实结构能否被维持是备受结构生物学家关注的问题。大肠杆菌甘油二脂激酶(DAGK)是一个很重要的三跨膜蛋白，其三维结构已经被液体核磁共振和X-Ray晶体衍射的方法在去垢剂胶束或脂质立方相中所解析，然而由于环境的不同，得到的结构差别很大，并且这两种结构都不是在DAGK的天然膜环境中进行解析的。固体核磁共振技术可以在接近膜蛋白天然环境的磷脂双层膜中解析其三维结构，是测定与证实膜蛋白结构的有力工具。本项目拟采用固体核磁共振技术在大肠杆菌磷脂膜的环境下对DAGK的三维结构进行解析，并分析不同环境下DAGK活性区域的结构变化，阐释膜蛋白结构与功能对膜环境的依赖性。	The structures of membrane proteins are profoundly influenced by membrane–protein interactions. To date, more than 90% structures of membrane protein in the PDB have been determined in membrane mimetic environments-detergent micelles. However, it is very difficult to obtain membrane mimetic environments that support the native structure and function of a membrane protein. Escherichia coli diacylglycerol kinase (DAGK) is a very important transmembrane protein of which three dimensional structure has been determined in detergent micelles or lipid cubic phase by solution-state NMR or X-Ray crystallography. Due to the different membrane mimetic environments, the two structures differ obviously. Solid-state NMR is a powerful tool for studying structures of membrane proteins in the native-like membrane environments. This project aims to use Solid-state NMR to determin the sturcture of DAGK in Escherichia coli total lipids bilayer. Then, we will expain the influence of membrane environments on membrane protein structure and function by comparation the structures of DAGK active domain in different membrane environments.	助理研究员
+与ALS/FTD相关联的C9orf72六核苷酸重复扩增形成G-四链体的结构研究	31500604	青年科学基金项目	香港科技大学深圳研究院	周波	20	2015	核磁共振；G-四链体；C9orf72六核苷酸重复扩增；肌萎缩性侧索硬化症；额颞叶痴呆	是	2;0;0;0;0	404024	100175543	630	C050101	2016-01至2018-12	肌萎缩性侧索硬化症（ALS）和额颞叶痴呆（FTD）是严重的神经退行性疾病。在家族性或散发性ALS/FTD患者中，位于9号染色体第72个开放阅读框基因（C9orf72）的GGGGCC六核苷酸重复扩增（HRE）是最常见的遗传致病因子。以往研究表明，C9orf72 HRE无论是作为DNA或转录的RNA产物，均可折叠成具有不同结构的G-四链体，并与ALS/FTD的致病机理密切相关。由于缺乏相关G-四链体的高分辨率结构信息，C9orf72 HRE形成G-四链体的分子机理仍不清楚。本研究将利用核磁共振技术首次获取C9orf72 HRE DNA及RNA G-四链体的高分辨率结构，对于在ALS/FTD患者中由于此种结构导致的异常转录产物诱发疾病的分子机理提供极有价值的信息，并且为针对C9orf72 HRE G-四链体设计小分子用以靶向调节ALS/ FTD的发病机制奠定必要的结构学基础。	Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) are devastating neurological diseases. Abnormal expansion of a hexanucleotide repeat, (GGGGCC)n, is the most common genetic cause of familial and sporadic forms of ALS and FTD. This nucleotide repeat element is located in a non-protein-coding region of the C9orf72 gene. Previous studies suggested that the C9orf72 hexanucleotide repeat expansion (HRE), either as DNA or the transcribed RNA, can fold into G-quadruplexes with distinct structures. It could also form transcriptionally induced RNA-DNA hybrids known as R-loops. These structural polymorphisms lead to C9orf72 HRE-containing abortive transcripts, which may aggregate and form RNA foci in patient cells. Despite the critical connection of C9orf72 HRE G-quadruplexes to the pathogenic mechanism of C9orf72 HRE-linked ALS/FTD, the molecular basis of G-quadruplex formation by C9orf72 HRE remains elusive..In this project, we plan to perform systematic biochemical and structural characterizations for C9orf72 HRE G-quadruplexes. First, we will determine the 3D structure of G-quadruplex formed by the C9orf72 HRE DNA. In our preliminary study, we successfully obtained a homogenous DNA sample, d(GGGGCC)4, which favored a monomeric G-quadruplex fold. We have determined the topology of this G-quadruplex DNA using the nuclear magnetic resonance (NMR) approach. It forms a chair-type G-quadruplex with a four-layer antiparallel G-tetra core and three edgewise loops, which is distinct from known structures of chair-type G-quadruplexes. We will further resolve its detailed structure using NMR techniques. We have also successfully obtained a homogeneous C9orf72 HRE RNA sample with sufficient quality for NMR structure determination. Unlike the monomeric d(GGGGCC)4 DNA, this RNA, r(GGGGCC)GGGG, is an asymmetric dimer. We will perform more NMR studies to obtain its 3D structure. As no structure of the C9orf72 HRE G-quadruplex has ever been solved, the structural information of C9orf72 HRE DNA/RNA G-quadruplexes to be obtained in the current project will provide valuable insights into the molecular mechanism of abortive transcripts formation by C9orf72 HRE and RNA foci appearance in ALS/FTD patients. The outcome of the proposed research will not only provide insight into the molecular mechanism underlying the C9orf72 HRE G-quadruplex formation in the etiology of ALS/FTD, but may also lay the necessary basis for designing small molecules that therapeutically target C9orf72 HRE G-quadruplexes for the modulation of ALS/FTD pathogenesis.	副研究员
+Sema-Plexin信号通路中FARP2的结构与功能研究	31500605	青年科学基金项目	华中科技大学	贺晓静	21	2015	蛋白质结构；相互作用；轴突导向	是	2;0;0;0;0	100113	100154722	630	C050101	2016-01至2018-12	神经系统的精确发育发展离不开轴突导向。神经细胞生长椎上的受体接受环境中的轴突导向因子传递的信号，经过一系列蛋白的传递，最后作用于细胞骨架蛋白，从而影响生长椎的走向。Semaphorin-Plexin 通路是其中重要的信号通路之一，我们的研究重点是这一通路中plexin的下游互作蛋白FARP2。FARP2 N端的FERM结构域介导它与Plexin之间的相互作用，但是二者之间的互作模式与分子机制还不清楚。本项目将利用晶体生物学，生物化学，细胞生物学等手段，在结构与功能上研究FARP2及其与Plexin的互作关系和分子调控机制，为进一步理解Sema-Plexin通路下游信号传导机制提供分子依据。我们之前的结构生物学研究发现FARP2 的DH-PH-PH结构域是一种以自我抑制构象存在的小GTP酶的鸟核苷酸交换因子(GEF)，本项目将进一步探讨如何激活FARP2的GEF活性。	英文摘要.The correct wiring of the nervous system relies on the precise axon guidance. During development of the nervous system, axons are guided to their proper targets by sensing a variety of extracellular cues in the local environment. The receptor protein on the neuronal growth cones which is located at the tip of the growing axon, recognizes guidance cues. The signal finally selectively alters the stability of the actin cytoskeleton and microtubules that determine the rate and direction  of   axon  extension.  Semaphorin-Plexin  is  one  of  the  classic ligand/receptor systems involved in this process， and we will focus on FARP2, which is a downstream partner of Plexin A1. FARP2 interacts with Plexin A1 though its N terminal FERM domain, but how they bind is still not clear. We are using  the  combination  of  protein  X-ray  crystallography,  biochemical techniques and cell based assay to study the structure and function of FARP2 and its interaction and regulation with Plexin A1. Our research will help us to understand the molecular regulation mechanisms of downstream signal transduction of Sema-plexin pathway.  C terminal domain DH-PH-PH of FARP2 is an auto-inhibited Guanine nucleotide exchange factor (GEF) based on our previous studies, and we will study how to active GEF activity further.	教授
+Tip49a/Tip49b及其相关复合物的冷冻电镜结构研究	31500606	青年科学基金项目	德州学院	宋峰	20	2015	冷冻电镜；单颗粒三维重构；蛋白复合物组装	是	4;0;0;0;0	400969	100181269	630	C050101	2016-01至2018-12	Tip49a和Tip49b是AAA+超家族的两个蛋白，它们保守地存在于从酵母到人的多个物种中，在细胞内通常以复合物的形式存在。它们在DNA损伤修复、转录调控、snoRNP成熟、染色质重塑等生命活动中发挥重要的调控作用，但迄今为止仍然没有Tip49a/Tip49b全长蛋白相关复合物的结构报道。本研究拟主要应用冷冻电镜单颗粒三维重构技术解析人源Tip49a/Tip49b及其参与形成的两种高级复合物（R2TP、Tip49a/Tip49b-核小体）的高精度三维结构，并结合生化实验确定Tip49a/Tip49b在两种高级复合物中的作用。本项目的研究成果将为理解Tip49a/Tip49b在snoRNP组装（R2TP复合物）和ATP依赖的染色质重塑（Tip49a/Tip49b-核小体复合物）中的工作机制提供可靠的结构信息。	Tip49a and Tip49b are two structurally and functionally highly related proteins that belong to the AAA+ (ATPase Associated with diverse cellular Activities) superfamily. They are existed in many species of which ranging from yeast to human. Both Tip49a and Tip49b are conserved components of various multi-subunit complexes, which are linked to a wide range of cellular processes, such as DNA damage response, transcription regulation, snoRNP biogenesis and ATP-dependent chromatin remodeling. Despite their diverse roles, there is no available high resolution structure of full-length Tip49a/Tip49b protein complex. The mainly purpose of our research is to reveal the high resolution structures of dodecameric Tip49a/Tip49b and determine their functions in two larger complexes which containing them, R2TP and Tip49a/Tip49b-nucleosome complex, by using cryo-EM single particle analysis combining with biochemical and biophysical techniques. Our research will provide insights into the structural basis of Tip49a/Tip49b in mediating snoRNP biogenesis(R2TP complex) and ATP-dependent chromatin remodeling(Tip49a/Tip49b-nucleosome complex).	教授
+结核分枝杆菌分枝菌酸合成途径脱水酶HadABC复合物与多种抗结核抑制剂的结构和功能研究	31500607	青年科学基金项目	中国科学院上海生命科学研究院	李俊	20	2015	结核分枝杆菌；晶体结构；分枝菌酸；脱水酶；药物靶点	是	3;0;0;0;0	201022	100175031	630	C050101	2016-01至2018-12	结核病是目前世界上致死率最高、传播范围最广的细菌性疾病。结核分枝杆菌是引发结核病的病原菌，由于耐多药菌株（MDR-TB）和广泛耐药菌株（XDR-TB）的出现，使得现有药物的治疗几乎失效。因此，寻找新的药物靶点以及研究全新作用机制的强力抗结核药物已经成为迫在眉睫的重要任务。由致密的分枝菌酸层构成的细胞壁使得结核分枝杆菌可以逃避免疫攻击和有害物质入侵从而能够存活。脱氢酶HadAB和HadBC是II型分枝菌酸脂链延伸系统（FAS-II）中最晚被发现的两对复合物，也是一线药物异烟肼靶点InhA的下游蛋白。迄今为止，其三维结构和催化机制尚不清楚。本研究项目可以填补这方面的空白，从分子水平上推进其酶活机制的研究；而HadABC与黄酮类抑制剂和抗结核药物Isoxyl、Thiacetazone复合物结构研究将揭示其抗结核的抑制机制，对基于HadABC的抗结核药物开发提供重要线索和可靠的结构生物学基础。	Tuberculosis (TB) is the most lethal and widely spread bacterial infectious disease over the world, mainly caused by the pathogenic Mycobacterium tuberculosis (Mtb). Seriously, the emergence of Multi-drug resistant TB (MDR-TB) and extensively drug resistant TB (XDR-TB) make currently used drugs ineffective to cure TB. Therefore, developing novel and effective anti-TB drugs following research of newly found drug targets has already been an urgent and important mission now. Mtb is hard to kill under host immune attack and survives from toxicant invasion because of the dense and hydrophobic mycolic acid layer of cell wall. Both of HadAB and HadBC were the dehydratases, which were the last and latest identified piece of the type II fatty acid synthesis (FAS-II) system, involved in the elongation of mycolic acid chain. The importance of mycolic acid for Mtb makes all the enzymes in this synthesis pathway potential drug targets including HadAB and HadBC. In fact, they were exact downstream enzymes of InhA, an approved target of currently first-line drug isoniazid. So far as we know, there are no crystal structures of HadAB and HadBC reported and the knowledge of catalytic mechanism is unclear as well. Thus, our research will fill in these gaps by deepening our understanding of it enzymatic catalysis from molecular perspective. Our research also aims to unveil inhibition mechanisms by studying the complex structures of HadABC with either flavonoid inhibitors or anti-TB drugs Isoxyl and Thiacetazone, which will lay sound structural basis and provide important clues for the anti-TB drug development.	副研究员
+单颗粒低温透射电镜高分辨率数据收集用支持膜的研究	31500608	青年科学基金项目	中国科学院生物物理研究所	黄小俊	20	2015	冷冻电镜成像技术；单颗粒三维重构；单颗粒冷冻电镜法	是	0;0;0;0;2	100067	100172851	630	C050101	2016-01至2018-12	单颗粒低温透射电镜技术发展至今，最大的瓶颈在于样品制备。而样品制备不可或缺的耗材是透射电镜载网。透射电镜载网（特别是覆在其上的支持膜）的亲水性能，机械性能，导电性能等直接影响着制备样品的质量及数据收集效率。本项目在已自主研制并应用的GIG微阵列碳支持膜的基础上，继续研发更符合实际需要的特定厚度、孔径及孔间距的微阵列支持膜，并以提升支持膜的导电性为目标以开发出第二代的该系列微阵列支持膜。最终将第二代的微阵列支持膜应用到低温透射电镜技术中，降低电子束引发的图像漂移状况，提升单颗粒低温透射电镜成像质量和数据收集效率。	Single particle cryo electron microscopy develops very fast these years. The bottle neck of this technique is at sample preparation. Among all those important factors of sample preparation, e.g. protein purity, concentration, rigidity et al., the properties of TEM grid, to be specific, the properties of supporting film on the TEM grid, is essential to preparing a good cryo sample. Hydrophilicity, strong mechanical strength, high conductivity of the supporting film affect the quality of prepared cryo sample and the efficiency of data collection. Based on the self-developed amorphous carbon film with fixed-pattern micro array (brand name GIG), this study aims to develop more suitable supporting films for cryoTEM usage. It includes designing suitable film thickness, hole size, spacing between hole which leads to high efficiency data collection, and increasing the conductivity of the supporting film at liquid nitrogen temperature which reduces the beam induce movement and enhances the quality of cryoEM images.	高级工程师
+干扰素诱导蛋白IFIT/ISG56家族抗病毒功能的结构生物学研究	31500609	青年科学基金项目	中国科学院生物物理研究所	冯峰	20	2015	IFIT/ISG56家族蛋白；抗病毒；天然免疫	是	1;0;0;0;0	100067	100218232	630	C050101	2016-01至2018-12	病原体和干扰素能够诱导ISG56/IFIT 家族蛋白的表达, 它们不仅具有抗病毒作用，而且还参与调节细胞的免疫反应。前期我们在国际上率先解析了该家族成员的晶体结构，并且通过结构信息证实了其抗病毒功能与核酸结合能力有关，但是其背后的分子机制尚不明确。本项目拟通过结构生物学结合细胞生物学的手段，在已获得的研究结果基础上系统地开展ISG56/IFIT 家族各个成员的抗病毒和免疫功能的分子机制的研究，包括比较家族成员之间的晶体结构差异；明确识别和结合核酸的序列和结构的特异性；检测在免疫反应信号通路中相互作用的分子，最终揭示家族各成员选择性激活表达的条件和特异性抗病毒的原因。本项目的研究成果将对宿主抗病毒天然免疫领域的研究以及相应的免疫临床治疗具有重要的理论和现实意义。	ISG56/IFIT family proteins，which be induced by interferon and pathogen，have antiviral functions and can regulate cellular immune response. Previously, we first solved the crystal structure of ISG56/IFIT family proteins and discovered that their antiviral functions are related to their ability to recognize nucleotides. However, the molecular mechanism remains unknown. In this project, we aim to reveal the mechanism of ISG56/IFIT proteins using structural and cellular biology methods. Base on the information on crystal structure differences, nucleic acid recognitions, binding partners in innate immune pathway, we try to propose the mechanism of specificity of ISG56/IFIT family proteins' antiviral functions. Our results will deepen people's understanding on innate immune response and provide practical significance on clinical treatment.	博士后
+Wnt信号通路中β-catenin及其细胞核内共激活因子复合物的结构生物学研究	31500610	青年科学基金项目	中国科学院生物物理研究所	孙伟	20	2015	蛋白质；相互作用；晶体筛选；结构解析；分子置换	是	1;0;0;0;0	100067	100045287	630	C050101	2016-01至2018-12	Wnt/β-catenin信号通路的过度激活会导致许多癌症的发生。β-catenin是该通路上的中心效应分子，它的表达上调是这些癌症发生的驱动因素。在细胞核内，多种共激活因子与β-catenin相互作用，共同激活下游肿瘤促进因子如cyclin-D和c-Myc的转录，其中M1型叉头框蛋白（FoxM1）和PCNA相关因子（PAF）就是其中两个。FoxM1促进β-catenin在细胞核内的定位，并可以促进Wnt应激基因的表达，在人类的多种肿瘤（比如神经胶质瘤）中都有过表达。PAF则在结直肠癌和肠干细胞中特异表达。因为β-catenin-FoxM1和β-catenin-PAF复合体的形成是Wnt/β-catenin下游的重要事件，对肿瘤的发生及恶化起重要作用，我们计划对它们开展结构生物学研究，以便阐释相关癌症的发生机理，并为人类癌症治疗提供新的思路。	Hyperactivation of the canonical Wnt/β-catenin signaling pathway can cause many types of cancers. β-catenin is the central effector of this signaling pathway, and its upregulation is a driving factor for these cancers. In the nucleus, many coactivators interact with β-catenin, activating transcription of downstream tumor-promoting factors such as cyclin-D and c-Myc. Forhead box protein M1 type (FoxM1) and PCNA-associated factor (PAF) are two β-catenin-specific transcriptional coactivators. FoxM1 promotes β-catenin nuclear localization and induces expression of Wnt responsive genes, and is overexpressed in many cancer types, including glioma. As to PAF, it is specifically expressed in colon cancer and intestine stem cells.  Because formations of β-catenin-FoxM1 and β-catenin-PAF complex are critical events downstream of Wnt/β-catenin signaling pathway, which play vital roles in tumorigenesis and metastasis of many cancers, we embark on investigating the interactions between β-catenin and FoxM1/PAF employing structural biological methods.  We aim to elucidate the molecular mechanism of tumorigenicity and try to provide novel insights into the therapy of human cancers.	博士后
+应用电子顺磁共振技术探究结核分枝杆菌分泌系统内膜蛋白Rv3882c跨膜结构域的结构特征	31500611	青年科学基金项目	中国科学院合肥物质科学研究院	于璐	20	2015	分枝杆菌分泌系统；膜蛋白；位点特异性自旋标记；电子顺磁共振；结构测定	是	2;0;0;0;0	100212	100134186	630	C050101	2016-01至2018-12	结核分枝杆菌的ESX-1分泌系统能使菌体分泌的致病因子、存活因子等蛋白质穿过其高度疏水致密的细胞被膜，对结核分枝杆菌的毒力和存活极为关键。因此，有关ESX-1分泌系统相关组成蛋白的结构分析对于理解结核杆菌感染机制具有非常重要的意义。Rv3882c蛋白是ESX-1分泌系统中一种重要的内膜蛋白，可能与其他组成蛋白共同形成通道类复合物，负责转运底物穿过细胞被膜，但目前其空间结构和确切的生物学功能尚不明确，仍亟待研究。本项目将结合位点特异性自旋标记与电子顺磁共振技术，通过获取Rv3882c蛋白跨膜结构域的运动性信息、易趋性信息以及在膜环境中的取向信息，综合分析得到Rv3882c蛋白跨膜结构域在膜环境中的三维结构模型。本项目的顺利开展，将为Rv3882c蛋白的结构研究提供重要依据，有助于进一步阐明结核分枝杆菌的分泌系统与致病机制，也为应用电子顺磁共振技术研究其他膜蛋白结构提供方法与思路。	The ESX-1 secretion system of Mycobacterium tuberculosis serves to secrete proteins, such as virulence factors and survival factors, across its highly hydrophobic and poorly permeable cell envelop, which is crucial for the virulence and survival of Mycobacterium tuberculosis. Therefore, structural investigation on component proteins of ESX-1 secretion system is very important for understanding the infection mechanisms of Mycobacterium tuberculosis. Rv0082c is a very important membrane protein of ESX-1 secretion system and is located on the inner membrane of Mycobacterium tuberculosis. It was predicted that Rv3382c forms a channel-like complex with other proteins and functions to transport the substrates across the mycobacterial cell envelope. However, the structure and function of this protein is still unclear. In this proposal, we are trying to characterize the structure of the transmembrane domain of membrane protein Rv3882c by combing Site Directed Spin Labelling (SDSL) technology and Electron Paramagnetic Resonance (EPR) spectroscopy. The acquired mobility, accessibility and orientation information in membrane will be integrated to derive a three dimensional structural model of the transmembrane domain of Rv3882c. Successful implementation of this project will not only yield valuable information for structural determination of Rv3882c, but also provide deeper insights of the protein secretion system and pathogenic mechanism of Mycobacterium tuberculosis. Also, this project will provide method of using EPR as the tool for structural studies of other membrane proteins.	副研究员
+真核生物mRNA转录出核复合物TREX-1的结构与功能研究	31500612	青年科学基金项目	许昌学院	苏测洋	20	2015	mRNA转录出核复合物；THO复合物；蛋白质结构生物学；X-射线晶体学；冷冻电镜	是	0;0;0;0;0	400411	100181698	630	C050101	2016-01至2018-12	真核生物mRNA转录出核复合物TREX-1广泛存在于从酵母到哺乳动物中，参与mRNA的转录、转录后加工和出核运输等一系列过程。有报道指出，TREX-1复合物组分在很多癌症组织中检测到表达异常。TREX-1复合物在真核生物中保守性较高，酵母源TREX-1复合物由Sub2、Yra1和THO复合物组成，人源TREX-1复合物由Uap56、Yra1以及人源THO复合物组成。目前，缺乏TREX-1复合物的高分辨率三维结构，这极大的阻碍了对其参与pre-mRNA加工分子机理的深入研究。我们之前的研究通过昆虫杆状病毒体外重组表达获得了高纯度的酵母源THO复合物。在此基础上，本项目拟对酵母和人源的TREX-1复合物进行组装与纯化，通过结合蛋白质X射线晶体学和冷冻电镜技术，以期获得TREX-1复合物高分辨率三维结构，并辅以生物化学和细胞生物学技术，研究其组装及参与mRNA出核的分子机制。	Eukaryotic mRNA TRanscription/EXport complex-1 (TREX-1 complex) is evolutionarily conserved multi-protein complex from yeast to human, participating in mRNA transcription, post-transcription processing and export. Previous report indicated that different protein component of TREX-1 complex has dysregulated expressed in different cancer specimens. Yeast TREX-1 complex consists Sub2, Yra1 and THO complex, while human TREX-1 complex consists Uap56 (yeast Sub2 homologous protein), Aly (yeast Yra1 homologous protein) and human THO complex. The detail mechanism of how TREX-1 complex participate pre-mRNA maturation and export is still obscurity, due to the miss of high-resolution 3D structural model of TREX-1 complex. In previous study, we get highly purified yeast THO complex through recombinant baculovirus expression system. Based on these, we try to reconstitute yeast and human TREX-1 complex in vivo and in vitro, through protein X-ray crystallography and cyro-EM technology, aim to get high-resolution 3D structure of TREX-1 complex. We also try to use biochemical and cell biology method to investigate the molecular mechanism of TREX-1 assembling and its participation mRNA export.	讲师
+一种新的葡萄糖脱氢酶FAD-GDH的晶体结构与催化机制研究	31560244	地区科学基金项目	遵义医科大学	杨愈丰	40	2015		否	0;0;0;0;0			631	C050101	2016-01至2019-12			
+高等植物PSII-LHCII超复合物的三维结构研究	31570724	面上项目	中国科学院生物物理研究所	曹鹏	70	2015		否	0;0;0;0;0			218	C050101	2016-01至2019-12			
+铁吸收调控蛋白Fur的复合物结构和识别机制研究	31570725	面上项目	中国农业大学	陈忠周	65	2015		否	0;0;0;0;0			218	C050101	2016-01至2019-12			
+中介体核心复合物调控RNA聚合酶II的结构机制研究	31570726	面上项目	中国科学技术大学	王雪娟	60	2015		否	0;0;0;0;0			218	C050101	2016-01至2019-12			
+基于冷冻电镜的呼肠孤病毒转录的分子机制研究	31570727	面上项目	清华大学	程凌鹏	62	2015		否	0;0;0;0;0			218	C050101	2016-01至2019-12			
+肺炎链球菌荚膜多糖合成途径的结构酶学	31570728	面上项目	中国科学技术大学	周丛照	62	2015		否	0;0;0;0;0			218	C050101	2016-01至2019-12			
+核小体水平上组蛋白修饰酶和组蛋白密码识别因子参与表观遗传调控的分子机理研究	31570729	面上项目	北京师范大学	王占新	65	2015		否	0;0;0;0;0			218	C050101	2016-01至2019-12			
+冷冻电镜数据采集和实时电子显微图像处理技术研究	31570730	面上项目	清华大学	李雪明	70	2015		否	0;0;0;0;0			218	C050101	2016-01至2019-12			
+核小体组蛋白H4被picNuA4复合物选择性乙酰化的结构基础	31570731	面上项目	清华大学	陈柱成	62	2015		否	0;0;0;0;0			218	C050101	2016-01至2019-12			
+小分子热休克蛋白的结构与作用机制	31570732	面上项目	北京大学	尹长城	65	2015		否	0;0;0;0;0			218	C050101	2016-01至2019-12			
+ABC转运蛋白的结构与功能研究	31570733	面上项目	清华大学	杨茂君	65	2015		否	0;0;0;0;0			218	C050101	2016-01至2019-12			
+细菌外源基因抑制因子的结构与功能研究	31570734	面上项目	北京大学	夏斌	70	2015		否	0;0;0;0;0			218	C050101	2016-01至2019-12			
+分泌系统内新型激酶的结构和底物识别机制研究	31570735	面上项目	北京大学	肖俊宇	62	2015		否	0;0;0;0;0			218	C050101	2016-01至2019-12			
+衣原体III型分泌系统结构的低温电镜研究	31570736	面上项目	中山大学	张勤奋	60	2015		否	0;0;0;0;0			218	C050101	2016-01至2019-12			
+人的SMN复合物识别snRNA调控snRNP装配的结构生物学研究	31570737	面上项目	中国科学技术大学	许超	62	2015		否	0;0;0;0;0			218	C050101	2016-01至2019-12			
+光合玫瑰菌核心光合复合体的结构与功能研究	31570738	面上项目	杭州师范大学	徐晓玲	62	2015		否	0;0;0;0;0			218	C050101	2016-01至2019-12			
+神经肽Y受体NPY1R的结构生物学研究	31570739	面上项目	中国科学院上海药物研究所	吴蓓丽	70	2015		否	0;0;0;0;0			218	C050101	2016-01至2019-12			
+具有新颖催化活性的细胞色素P450酶TxtE和甲基转移酶TleD的晶体结构和功能研究	31570740	面上项目	中国科学院上海应用物理研究所	郁峰	62	2015		否	0;0;0;0;0			218	C050101	2016-01至2019-12			
+Liprin-α介导的神经突触形成中活性区组装机制的研究	31570741	面上项目	南方科技大学	魏志毅	62	2015		否	0;0;0;0;0			218	C050101	2016-01至2019-12			
+基于冷冻电镜二十面体对称失配三维重构的腺病毒结构研究	31570742	面上项目	湖南师范大学	刘红荣	62	2015		否	0;0;0;0;0			218	C050101	2016-01至2019-12			
+糖原代谢关键蛋白质的结构和功能研究	31570743	面上项目	中国科学院上海生命科学研究院	向嵩	60	2015		否	0;0;0;0;0			218	C050101	2016-01至2019-12			
+蛋白质晶体学结构测定新技术研究	31570744	面上项目	中国科学院高能物理研究所	董宇辉	65	2015		否	0;0;0;0;0			218	C050101	2016-01至2019-12			
+内吞性胶原蛋白受体Endo180 的结构研究	31570745	面上项目	福州大学	袁彩	62	2015		否	0;0;0;0;0			218	C050101	2016-01至2019-12			
+线粒体解偶联蛋白UCP1的结构和功能解析	31570746	面上项目	中国科学院上海生命科学研究院	周界文	65	2015		否	0;0;0;0;0			218	C050101	2016-01至2019-12			
+参与基因表达转录后调控的重要蛋白质-RNA复合物的结构与功能研究	31570747	面上项目	中国科学院生物物理研究所	刘超培	60	2015		否	0;0;0;0;0			218	C050101	2016-01至2019-12			
+磷脂酰肌醇合成酶的结构与功能	31570748	面上项目	中国科学院上海生命科学研究院	李典范	62	2015		否	0;0;0;0;0			218	C050101	2016-01至2019-12			
+负链RNA病毒聚合酶的结构和功能机制研究	31530015	重点项目	中国科学院生物物理研究所	刘迎芳	292	2015		否	0;0;0;0;0			220	C050101	2016-01至2020-12			
+染色体的结构与功能研究	31525007	国家杰出青年科学基金	上海交通大学	雷鸣	350	2015		否	0;0;0;0;0			429	C050101	2016-01至2020-12			
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