Mechanism of Voltage Gating in Potassium Channels
Mechanism of Voltage Gating in Potassium Channels
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DOI：
10.1126/science.1216533
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发表时间：
2012-04-13
期刊：
影响因子：
56.9
通讯作者：
Shaw, David E.
中科院分区：
文献类型：
--
作者：
Jensen, Morten O.;Jogini, Vishwanath;Shaw, David E.
离子通道电压门控的机制-通道如何响应电压变化而打开和关闭-自从Hodgkin和Huxley开创性地发现神经传导的关键是离子流过细胞膜以来一直存在争议。利用全原子分子动力学模拟，我们展示了电压门控钾通道（KV）如何在激活和失活状态之间切换。在失活时，孔疏水性塌陷迅速停止离子流动。随后的电压敏感域（VSD）松弛，包括向内，15埃的S4-螺旋运动，完成过渡。在活化时，向外的S4运动收紧VSD-孔接头，扰乱接头-S6-螺旋包装。波动允许水，然后钾离子，重新进入孔;连接子-S6重新填充稳定开放的孔。我们提出了一个机制模型的钠/钾/钙电压门控离子通道超家族，调和明显相互矛盾的实验数据。
The mechanism of ion channel voltage gating-how channels open and close in response to voltage changes-has been debated since Hodgkin and Huxley's seminal discovery that the crux of nerve conduction is ion flow across cellular membranes. Using all-atom molecular dynamics simulations, we show how a voltage-gated potassium channel (KV) switches between activated and deactivated states. On deactivation, pore hydrophobic collapse rapidly halts ion flow. Subsequent voltage-sensing domain (VSD) relaxation, including inward, 15-angstrom S4-helix motion, completes the transition. On activation, outward S4 motion tightens the VSD-pore linker, perturbing linker-S6-helix packing. Fluctuations allow water, then potassium ions, to reenter the pore; linker-S6 repacking stabilizes the open pore. We propose a mechanistic model for the sodium/potassium/calcium voltage-gated ion channel superfamily that reconciles apparently conflicting experimental data.