The sliding-helix voltage sensor: mesoscale views of a robust structure-function relationship.
The sliding-helix voltage sensor: mesoscale views of a robust structure-function relationship.
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DOI：
10.1007/s00249-012-0847-z
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发表时间：
2012-09
影响因子：
2
通讯作者：
Nonner, Wolfgang
中科院分区：
文献类型：
--
作者：
Peyser, Alexander;Nonner, Wolfgang
电压门控离子通道的电压感受器域是活细胞电兴奋性的基础。我们模拟的VS域的中尺度模型，以确定其一些物理元素的功能后果。我们的中尺度模型是基于VS电荷，线性振荡和全身运动，适用于S4“滑动螺旋”。电压箝位边界条件下的静电一致使用边界元法求解。基于静电构型能，位移电荷和膜电压之间的实验观察到的关系的物理机械预期进行了预测。该模型的后果进行了调查的变化：S4配置（α-和310-螺旋），与S4电荷，蛋白质极化率，门控通道的几何形状，S4电荷的筛选浴，和固定的电荷位于浴界面。滑动螺旋VS域在探索的参数空间中具有固有的静电稳定性：弱电介质区域中存在的反电荷总是在该区域中保留等效的S4电荷，但允许滑动移动位移3至4 e0。这种运动对沿着路径的小能量变化（< 2kT）敏感，这取决于我们模拟中测试的许多静电参数。这些模拟显示了如何在沟道中调整位移电荷和电压之间的关系的斜率。
The voltage sensor (VS) domain of voltage-gated ion channels underlies electrical excitability of living cells. We simulate a mesoscale model of the VS domain to determine the functional consequences of some of its physical elements. Our mesoscale model is based on VS charges, linear dielectrics and whole-body motion, applied to an S4 ‘sliding helix’. The electrostatics under voltage-clamped boundary conditions are solved consistently using a boundary element method. Based on electrostatic configurational energy, statistical-mechanical expectations of the experimentally observable relation between displaced charge and membrane voltage are predicted. Consequences of the model are investigated for variations of: S4 configuration (α- and 310-helical), countercharge alignment with S4 charges, protein polarizability, geometry of the gating canal, screening of S4 charges by the baths, and fixed charges located at the bath interfaces. The sliding helix VS domain has an inherent electrostatic stability in the explored parameter space: countercharges present in the region of weak dielectric always retain an equivalent S4 charge in that region but allow sliding movements displacing 3 to 4 e0. That movement is sensitive to small energy variations (< 2kT) along the path dependent on a number of electrostatic parameters tested in our simulations. These simulations show how the slope of the relation between displaced charge and voltage could be tuned in a channel.
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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：
4.3
作者：
Bjelkmar, Par;Niemela, Perttu S.;Vattulainen, Ilpo;Lindahl, Erik
通讯作者：
Lindahl, Erik
影响因子：
56.9
作者：
Long, SB;Campbell, EB;MacKinnon, R
通讯作者：
MacKinnon, R
影响因子：
2.7
作者：
Doi, Masao
通讯作者：
Doi, Masao
影响因子：
56.9
作者：
Jensen, Morten O.;Jogini, Vishwanath;Shaw, David E.
通讯作者：
Shaw, David E.