Control of ion selectivity in potassium channels by electrostatic and dynamic properties of carbonyl ligands
Control of ion selectivity in potassium channels by electrostatic and dynamic properties of carbonyl ligands
复制标题
DOI：
10.1038/nature02943
复制
发表时间：
2004-10-14
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：
Noskov, SY;Bernèche, S;Roux, B
钾通道对于维持细胞膜上的正常离子平衡是必不可少的。这种功能的核心是这种通道能够以接近扩散限制的速率支持跨膜离子传导，同时区分K+超过Na+一千倍。这种选择性的产生是因为K+离子转移到通道孔中是能量上有利的，这一特征通常归因于K+离子和刚性窄孔内衬的羰基之间的结构精确配合（1）。但蛋白质是相对灵活的结构（2，3），经历快速的热原子波动大于K+和Na+之间的离子半径的微小差异。在这里，我们提出的钾通道KcsA，这表明，羰基配合离子在窄孔的分子动力学模拟确实是非常动态的（“液体样”），其固有的静电特性控制离子的选择性。这一发现强调了经典场强概念的重要性（4）。对K+的选择性被认为是由羰基排列的柔性波动孔的强大特征。
Potassium channels are essential for maintaining a normal ionic balance across cell membranes. Central to this function is the ability of such channels to support transmembrane ion conduction at nearly diffusion-limited rates while discriminating for K+ over Na+ by more than a thousand-fold. This selectivity arises because the transfer of the K+ ion into the channel pore is energetically favoured, a feature commonly attributed to a structurally precise fit between the K+ ion and carbonyl groups lining the rigid and narrow pore(1). But proteins are relatively flexible structures(2,3) that undergo rapid thermal atomic fluctuations larger than the small difference in ionic radius between K+ and Na+. Here we present molecular dynamics simulations for the potassium channel KcsA, which show that the carbonyl groups coordinating the ion in the narrow pore are indeed very dynamic ('liquid-like') and that their intrinsic electrostatic properties control ion selectivity. This finding highlights the importance of the classical concept of field strength(4). Selectivity for K+ is seen to emerge as a robust feature of a flexible fluctuating pore lined by carbonyl groups.