Molecular driving forces determining potassium channel slow inactivation
Molecular driving forces determining potassium channel slow inactivation
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DOI：
10.1038/nsmb1309
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发表时间：
2007-11-01
影响因子：
16.8
通讯作者：
Perozo, Eduardo
中科院分区：
文献类型：
--
作者：
Cordero-Morales, Julio F.;Jogini, Vishwanath;Perozo, Eduardo
K+通道经历时间依赖性的缓慢失活过程，在调节细胞兴奋性中起关键作用。在这里，我们表明，在原核质子门控K+通道KcsA中，选择性过滤器及其邻近孔螺旋中残基之间的氢键数量和强度决定了C型失活的速率和程度。通道激活后，在位置Glu71和Asp80的残基之间的相互作用，促进过滤器收缩平行的渗透途径，影响K+结合位点，并推测废除离子传导。这两个位置之间的耦合导致它们的相互作用强度和失活状态的稳定性之间的定量相关性。真核细胞电压依赖性K+通道Kv1.2中的这些相互作用的工程表明，类似的机制原理适用于其他K+通道。这些观察结果为理解K+通道中C型失活提供了一个合理的物理框架。
K+ channels undergo a time-dependent slow inactivation process that plays a key role in modulating cellular excitability. Here we show that in the prokaryotic proton-gated K+ channel KcsA, the number and strength of hydrogen bonds between residues in the selectivity filter and its adjacent pore helix determine the rate and extent of C-type inactivation. Upon channel activation, the interaction between residues at positions Glu71 and Asp80 promotes filter constriction parallel to the permeation pathway, which affects K+-binding sites and presumably abrogates ion conduction. Coupling between these two positions results in a quantitative correlation between their interaction strength and the stability of the inactivated state. Engineering of these interactions in the eukaryotic voltage-dependent K+ channel Kv1.2 suggests that a similar mechanistic principle applies to other K+ channels. These observations provide a plausible physical framework for understanding C-type inactivation in K+ channels.