Structure of a bacterial voltage-gated sodium channel pore reveals mechanisms of opening and closing.
Structure of a bacterial voltage-gated sodium channel pore reveals mechanisms of opening and closing.
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DOI：
10.1038/ncomms2077
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发表时间：
2012
影响因子：
16.6
通讯作者：
中科院分区：
文献类型：
--
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钠门控离子通道响应离子流而打开和关闭。在这里，麦卡斯克等人。报告了细菌同系物的钠门控离子通道孔的开放结构，并通过与封闭结构的比较表明，C 末端螺旋的运动足以打开通道。电压门控钠通道是电信号传导所必需的重要膜蛋白。在人类中，它们是药物开发的关键目标。在这里，我们报告了 NavMs 开放通道构象的晶体结构，NavMs 是海洋细菌磁球菌属的细菌通道孔。 （菌株MC-1）。它与最近发表的相关细菌钠通道 (NavAb) 封闭形式的晶体结构不同，其内腔由于羧基端跨膜片段中心残基的弯曲/旋转而可通向细胞质表面。这会产生一个直径足够大的开放激活门，以允许水合钠离子通过。开放和封闭结构的比较为钠通道激活循环中存在的功能状态特征以及通道打开和关闭的机制提供了新的见解。
Sodium-gated ion channels open and close in response to the flow of ions. Here, McCusker et al. report the open structure of a sodium-gated ion channel pore from a bacterial homologue, and show, by comparison with the closed structure, that the movement of a C-terminal helix is sufficient to open the channel. Voltage-gated sodium channels are vital membrane proteins essential for electrical signalling; in humans, they are key targets for the development of pharmaceutical drugs. Here we report the crystal structure of an open-channel conformation of NavMs, the bacterial channel pore from the marine bacterium Magnetococcus sp. (strain MC-1). It differs from the recently published crystal structure of a closed form of a related bacterial sodium channel (NavAb) by having its internal cavity accessible to the cytoplasmic surface as a result of a bend/rotation about a central residue in the carboxy-terminal transmembrane segment. This produces an open activation gate of sufficient diameter to allow hydrated sodium ions to pass through. Comparison of the open and closed structures provides new insight into the features of the functional states present in the activation cycles of sodium channels and the mechanism of channel opening and closing.
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DOI：
10.1073/pnas.0711533105
发表时间：
2008-02-05
影响因子：
11.1
作者：
Clayton, Gina M.;Altieri, Steve;Morais-Cabral, Joao H.
通讯作者：
Morais-Cabral, Joao H.
影响因子：
64.8
作者：
Long, Stephen B.;Tao, Xiao;MacKinnon, Roderick
通讯作者：
MacKinnon, Roderick
影响因子：
56.9
作者：
Doyle, DA;Cabral, JM;MacKinnon, R
通讯作者：
MacKinnon, R
DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
DOI：
10.1107/s0907444904016427
发表时间：
2004-12-01
影响因子：
2.2
作者：
Blanc, E;Roversi, P;Bricogne, G
通讯作者：
Bricogne, G