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Crystal structure of an orthologue of the NaChBac voltage-gated sodium channel
文献类型：期刊论文
| 作者 | Zhang, Xu3,4,5; Ren, Wenlin3,4,5; DeCaen, Paul6,7; Yan, Chuangye3,4,5; Tao, Xiao8; Tang, Lin2; Wang, Jingjing9; Hasegawa, Kazuya1; Kumasaka, Takashi1; He, Jianhua2 |
| 刊名 | NATURE
 |
| 出版日期 | 2012-06-07 |
| 卷号 | 486期号:7401页码:130-U160 |
| ISSN号 | 0028-0836 |
| DOI | 10.1038/nature11054 |
| 文献子类 | Article |
| 英文摘要 | Voltage-gated sodium (Na-v) channels are essential for the rapid depolarization of nerve and muscle(1), and are important drug targets(2). Determination of the structures of Na-v channels will shed light on ion channel mechanisms and facilitate potential clinical applications. A family of bacterial Na-v channels, exemplified by the Na+-selective channel of bacteria (NaChBac)(3), provides a useful model system for structure-function analysis. Here we report the crystal structure of NavRh, a NaChBac orthologue from the marine alphaproteobacterium HIMB114 (Rickettsiales sp. HIMB114; denoted Rh), at 3.05 angstrom resolution. The channel comprises an asymmetric tetramer. The carbonyl oxygen atoms of Thr 178 and Leu 179 constitute an inner site within the selectivity filter where a hydrated Ca2+ resides in the crystal structure. The outer mouth of the Na+ selectivity filter, defined by Ser 181 and Glu 183, is closed, as is the activation gate at the intracellular side of the pore. The voltage sensors adopt a depolarized conformation in which all the gating charges are exposed to the extracellular environment. We propose that NavRh is in an 'inactivated' conformation. Comparison of NavRh with Na(v)Ab(4) reveals considerable conformational rearrangements that may underlie the electromechanical coupling mechanism of voltage-gated channels. |
| WOS关键词 | DEPENDENT K+ CHANNEL ; SWISS-MODEL ; SLOW INACTIVATION ; GATING CHARGE ; NMR SYSTEM ; ENVIRONMENT ; SOFTWARE ; SENSOR ; CRYSTALLOGRAPHY ; ACTIVATION |
| 资助项目 | Ministry of Science and Technology[2009CB918802] ; Ministry of Science and Technology[2011CB910501] ; Ministry of Science and Technology[2011CB911102] ; National Natural Science Foundation of China[31125009] ; National Natural Science Foundation of China[91017011] ; Tsinghua University[00000000] |
| WOS研究方向 | Science & Technology - Other Topics |
| 语种 | 英语 |
| WOS记录号 | WOS:000304854000042 |
| 出版者 | NATURE PUBLISHING GROUP |
| 源URL | [http://119.78.100.183/handle/2S10ELR8/278042]  |
| 专题 | 新药研究国家重点实验室 中科院受体结构与功能重点实验室 |
| 通讯作者 | Yan, Nieng |
| 作者单位 | 1.SPring 8, Japan Synchrotron Radiat Res Inst, Sayo, Hyogo 6795198, Japan 2.Chinese Acad Sci, Shanghai Inst Appl Phys, Shanghai 201204, Peoples R China; 3.Tsinghua Univ, Sch Life Sci, Struct Biol Ctr, State Key Lab Biomembrane & Membrane Biotechnol, Beijing 100084, Peoples R China; 4.Tsinghua Univ, Sch Med, Beijing 100084, Peoples R China; 5.Tsinghua Univ, Tsinghua Peking Ctr Life Sci, Beijing 100084, Peoples R China; 6.Childrens Hosp Boston, Dept Cardiol, Howard Hughes Med Inst, Boston, MA 02115 USA; 7.Harvard Univ, Sch Med, Dept Neurobiol, Boston, MA 02115 USA; 8.Rockefeller Univ, Howard Hughes Med Inst, Lab Mol Neurobiol & Biophys, New York, NY 10065 USA; 9.Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China; |
| 推荐引用方式 GB/T 7714 | Zhang, Xu,Ren, Wenlin,DeCaen, Paul,et al. Crystal structure of an orthologue of the NaChBac voltage-gated sodium channel[J]. NATURE,2012,486(7401):130-U160. |
| APA | Zhang, Xu.,Ren, Wenlin.,DeCaen, Paul.,Yan, Chuangye.,Tao, Xiao.,...&Yan, Nieng.(2012).Crystal structure of an orthologue of the NaChBac voltage-gated sodium channel.NATURE,486(7401),130-U160. |
| MLA | Zhang, Xu,et al."Crystal structure of an orthologue of the NaChBac voltage-gated sodium channel".NATURE 486.7401(2012):130-U160. |
入库方式： OAI收割
来源：上海药物研究所
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