Structural mechanism of voltage-dependent gating in an isolated voltage-sensing domain.
Structural mechanism of voltage-dependent gating in an isolated voltage-sensing domain.
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DOI：
10.1038/nsmb.2768
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发表时间：
2014-03
影响因子：
16.8
通讯作者：
Perozo E
中科院分区：
文献类型：
--
作者：
Li Q;Wanderling S;Paduch M;Medovoy D;Singharoy A;McGreevy R;Villalba-Galea CA;Hulse RE;Roux B;Schulten K;Kossiakoff A;Perozo E
跨膜电场对蛋白质运动的转导在细胞信号的产生和传播中起着重要的作用。电压敏感域（VSD）通过离散门控电荷对S4螺旋的重新取向来实现这些功能。在这里，从Ci-VSP的VSD的晶体结构被确定在两个，活性（上）和静息（下）构象。S4沿其主轴沿着移动约5 °，并伴随约60 °的旋转，与螺旋-螺杆浇口机制一致。这种运动通过螺旋S1和S3中的反电荷伴侣的变化而稳定，产生约1 eo的估计净电荷转移。门控电荷相对于“疏水垫圈”移动，该疏水垫圈电划分细胞内和细胞外隔室。EPR光谱证实了膜环境中S4运动的有限性质。这些结果提供了一个明确的机制，电压感知和机电耦合电压依赖性细胞活动的基础。
The transduction of transmembrane electric fields into protein motion plays an essential role in the generation and propagation of cellular signals. Voltage-sensing domains (VSD) carry out these functions through reorientations of S4 helix with discrete gating charges. Here, crystal structures of the VSD from Ci-VSP were determined in both, active (Up) and resting (Down) conformations. The S4 undergoes a ~5 Å displacement along its main axis accompanied by a ~60o rotation, consistent with the helix-screw gating mechanism. This movement is stabilized by a change in countercharge partners in helices S1 and S3, generating an estimated net charge transfer of ~1 eo. Gating charges move relative to a “hydrophobic gasket” that electrically divides intra and extracellular compartments. EPR spectroscopy confirms the limited nature of S4 movement in a membrane environment. These results provide an explicit mechanism for voltage sensing and set the basis for electromechanical coupling in voltage-dependent cellular activities.
DOI：
10.4161/chan.3.5.9697
发表时间：
2009-09
期刊：
Channels (Austin, Tex.)
影响因子：
--
作者：
Koag MC;Papazian DM
通讯作者：
Papazian DM