Open-state conformation of the KcsA K+ channel:: Monte Carlo normal mods following Simulations
Open-state conformation of the KcsA K+ channel:: Monte Carlo normal mods following Simulations
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DOI：
10.1016/j.str.2007.09.022
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发表时间：
2007-12-01
期刊：
影响因子：
5.7
通讯作者：
Jordan, Peter C.
中科院分区：
文献类型：
--
作者：
Miloshevsky, Gennady V.;Jordan, Peter C.
钾通道在关闭和开放状态之间波动。变铅青链霉菌(Streptomyces lividans，KCSA)K+通道的构象变化打开胞内孔洞的详细机制尚不清楚。应用蒙特卡罗简正波跟踪，我们发现门控包括TM2束的旋转和解绕，TM2螺旋的横向运动远离沟道轴，以及TM2束的消失。KCSA的开放构象显示出非常宽的内前庭，半径类似于5-7埃，内螺旋在A98-G99铰链处弯曲。计算的构象变化表明，自旋标记和X射线实验揭示了门控的不同阶段：转变开始于TM2螺旋的顺时针旋转，结束于最终状态，TM2弯曲铰接在残基A98-G99附近。计算结果和实验结果之间的一致性为通道内部孔隙的结构重排提供了原子水平的洞察。
Potassium channels fluctuate between closed and open states. The detailed mechanism of the conformational changes opening the intracellular pore in the K+ channel from Streptomyces lividans (KcsA) is unknown. Applying Monte Carlo normal mode following, we find that gating involves rotation and unwinding of the TM2 bundle, lateral movement of the TM2 helices away from the channel axis, and disappearance of the TM2 bundle. The open-state conformation of KcsA exhibits a very wide inner vestibule, with a radius similar to 5-7 angstrom and inner helices bent at the A98-G99 hinge. Computed conformational changes demonstrate that spin labeling and X-ray experiments illuminate different stages in gating: transition begins with clockwise rotation of the TM2 helices ending at a final state with the TM2 bend hinged near residues A98-G99. The concordance between the computational and experimental results provides atomic-level insights into the structural rearrangements of the channel's inner pore.