Mechanism of activation at the selectivity filter of the KcsA K+ channel
Mechanism of activation at the selectivity filter of the KcsA K+ channel
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DOI：
10.7554/elife.25844.001
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发表时间：
2017-10-10
期刊：
影响因子：
7.7
通讯作者：
Berneche, Simon
中科院分区：
文献类型：
--
作者：
Heer, Florian T.;Posson, David J.;Berneche, Simon
钾通道通过配体和/或膜电位打开。在电压门控K+通道和原核KcsA通道中，传导被认为是由于细胞内收缩的打开而导致的，该收缩阻止离子进入孔。另一方面，许多配体门控的K+通道缺乏这样的门，这表明它们可能被选择性过滤器内的变化激活，选择性过滤器是孔的细胞外侧的狭窄区域。使用分子动力学模拟和电生理学测量，我们表明，配体诱导的构象变化的KcsA通道中删除的选择性过滤器的空间限制，从而导致结构波动，降低K+亲和力，并增加离子渗透。选择性过滤器的这种激活可能是K+通道内的通用门控机制。在细胞内门水平的孔闭塞似乎是继发性的。
Potassium channels are opened by ligands and/or membrane potential. In voltage-gated K+ channels and the prokaryotic KcsA channel, conduction is believed to result from opening of an intracellular constriction that prevents ion entry into the pore. On the other hand, numerous ligand-gated K+ channels lack such gate, suggesting that they may be activated by a change within the selectivity filter, a narrow region at the extracellular side of the pore. Using molecular dynamics simulations and electrophysiology measurements, we show that ligand-induced conformational changes in the KcsA channel removes steric restraints at the selectivity filter, thus resulting in structural fluctuations, reduced K+ affinity, and increased ion permeation. Such activation of the selectivity filter may be a universal gating mechanism within K+ channels. The occlusion of the pore at the level of the intracellular gate appears to be secondary.