Energetics of ion conduction through the K+ channel
Energetics of ion conduction through the K+ channel
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DOI：
10.1038/35102067
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发表时间：
2001-11-01
期刊：
影响因子：
64.8
通讯作者：
Roux, B
中科院分区：
文献类型：
--
作者：
Bernèche, S;Roux, B
K+通道是一种跨膜蛋白，对神经冲动的传递是必不可少的。这些蛋白质在接近扩散极限的水平上传导K+离子的能力传统上是用协同机制来描述的，在协同机制中，离子通道吸引和离子-离子排斥具有补偿效应，因为几个离子同时以单列形式通过狭窄的孔道(1-4)。然而，这种机制的效率依赖于一种微妙的能量平衡--强大的离子通道吸引力必须被静电离子斥力完美地平衡。为了在原子水平上阐明离子传导的机制，我们根据KCSA K+通道(4)的X射线结构进行了分子动力学自由能模拟。这里我们发现离子传导涉及两个主态之间的跃迁，两个和三个K+离子分别占据选择性滤光片；这个过程让人想起Hodgkin和Keynes在1955年提出的‘敲击’机制(1)。最大自由能垒在2-3千卡摩尔(-1)数量级，表明离子传导过程受扩散的限制。离子-离子斥力虽然对快速传导是必不可少的，但被证明只在很短的距离内起作用。计算还表明，快速导电孔具有选择性。
K+ channels are transmembrane proteins that are essential for the transmission of nerve impulses. The ability of these proteins to conduct K+ ions at levels near the limit of diffusion is traditionally described in terms of concerted mechanisms in which ion-channel attraction and ion-ion repulsion have compensating effects, as several ions are moving simultaneously in single file through the narrow pore(1-4). The efficiency of such a mechanism, however, relies on a delicate energy balance-the strong ion-channel attraction must be perfectly counterbalanced by the electrostatic ion-ion repulsion. To elucidate the mechanism of ion conduction at the atomic level, we performed molecular dynamics free energy simulations on the basis of the X-ray structure of the KcsA K+ channel(4). Here we rnd that ion conduction involves transitions between two main states, with two and three K+ ions occupying the selectivity filter, respectively; this process is reminiscent of the 'knock-on' mechanism proposed by Hodgkin and Keynes in 1955(1). The largest free energy barrier is on the order of 2-3 kcal mol(-1), implying that the process of ion conduction is limited by diffusion. Ion-ion repulsion, although essential for rapid conduction, is shown to act only at very short distances. The calculations show also that the rapidly conducting pore is selective.