Ion permeation mechanism of the potassium channel
Ion permeation mechanism of the potassium channel
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DOI：
10.1038/35009114
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发表时间：
2000-04-20
期刊：
影响因子：
64.8
通讯作者：
Luzhkov, V
中科院分区：
文献类型：
--
作者：
Åqvist, J;Luzhkov, V
离子选择通道使离子通过细胞膜的特异性渗透，并为几种重要的生物学功能提供了基础；例如，神经系统中的电信号(1)。虽然有大量的电生理数据可用（1,2），但这些通道介导离子运输的分子机制仍然是一个重要的未解决的问题。利用最近确定的来自lividans链霉菌的代表性K+通道（KcsA）的晶体结构(3)，可以在微观水平上检查离子传导途径。K+通道利用多离子传导机制（1,2,4-6），并且三维结构也显示通道中存在多个离子。在这里，我们报告了分子动力学自由能摄动计算的结果，这些结果既建立了多离子传导机制的性质，又产生了通道的正确离子选择性。通过评价选择性滤光器所有相关占位态的能量学，我们发现有利的传导途径只涉及两个主要态之间的转换，自由差约为5千卡摩尔（-1）。其他假定的渗透途径可以被排除，因为它们会涉及能量过高的状态。
Ion-selective channels enable the specific permeation of ions through cell membranes and provide the basis of several important biological functions; for example, electric signalling in the nervous system(1). Although a large amount of electrophysiological data is available(1,2), the molecular mechanisms by which these channels can mediate ion transport remain a significant unsolved problem. With the recently determined crystal structure of the representative K+ channel (KcsA) from Streptomyces lividans(3), it becomes possible to examine ion conduction pathways on a microscopic level. K+ channels utilize multi-ion conduction mechanisms(1,2,4-6), and the three-dimensional structure also shows several ions present in the channel. Here we report results from molecular dynamics free energy perturbation calculations that both establish the nature of the multiple ion conduction mechanism and yield the correct ion selectivity of the channel. By evaluating the energetics of all relevant occupancy states of the selectivity filter, we rnd that the favoured conduction pathway involves transitions only between two main states with a free difference of about 5 kcal mol(-1). Other putative permeation pathways can be excluded because they would involve states that are too high in energy.