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钾离子通道(KcsA)选择性过滤器上的电压依赖性门控。

Voltage-dependent gating at the KcsA selectivity filter.

作者信息

Cordero-Morales Julio F, Cuello Luis G, Perozo Eduardo

机构信息

Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, Virginia 22906, USA.

出版信息

Nat Struct Mol Biol. 2006 Apr;13(4):319-22. doi: 10.1038/nsmb1070. Epub 2006 Mar 12.

Abstract

The prokaryotic K(+) channel KcsA, although lacking a 'standard' voltage-sensing domain, shows voltage-dependent gating that leads to an increase in steady-state open probability of almost two orders of magnitude between +150 and -150 mV. Here we show that voltage-dependent gating in KcsA is associated with the movement of approximately 0.7 equivalent electronic charges. This charge movement produces an increase in the rate of entry into a long-lived inactivated state and seems to be independent of the proton-activation mechanism. Charge neutralization at position 71 renders the channel essentially voltage-independent by preventing entry into the inactivated state. A mechanism for voltage-dependent gating at the selectivity filter is proposed that is based on the reorientation of the carboxylic moiety of Glu71 and its influence in the conformational dynamics of the selectivity filter.

摘要

原核生物钾离子通道KcsA虽然缺乏“标准”的电压感应结构域,但其呈现出电压依赖性门控,在+150 mV至 -150 mV之间,稳态开放概率增加了近两个数量级。我们在此表明,KcsA中的电压依赖性门控与约0.7个等效电子电荷的移动相关。这种电荷移动使进入长寿命失活状态的速率增加,并且似乎与质子激活机制无关。71位的电荷中和通过阻止进入失活状态使通道基本上不依赖电压。提出了一种基于选择性过滤器中谷氨酸71羧基部分的重新定向及其对选择性过滤器构象动力学影响的选择性过滤器电压依赖性门控机制。

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