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Ion selectivity in potassium channels

机译:钾离子通道中的离子选择性

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Potassium channels are tetrameric membrane-spanning proteins that provide a selective pore for the conduction of K+ across the cell membranes. One of the main physiological functions of potassium channels is efficient and very selective transport of K+ ions through the membrane to the cell. Classical views of ion selectivity are summarized within a historical perspective, and contrasted with the molecular dynamics (MD) simulations free energy perturbation (FEP) performed on the basis of the crystallographic structure of the KcsA phospholipid membrane. The results show that the KcsA channel does not select for K+ ions by providing a binding site of an appropriate (fixed) cavity size. Rather, selectivity for K+ arises directly from the intrinsic local physical properties of the ligands coordinating the cation in the binding site, and is a robust feature of a pore symmetrically lined by backbone carbonyl groups. Further analysis reveals that it is the interplay between the attractive ion-ligand (favoring smaller cation) and repulsive ligand-ligand interactions (favoring larger cations) that is the basic element governing Na+/K+ selectivity in flexible protein binding sites. Because the number and the type of ligands coordinating an ion directly modulate such local interactions, this provides a potent molecular mechanism to achieve and maintain a high selectivity in protein binding sites despite a significant conformational flexibility. (c) 2006 Elsevier B.V. All rights reserved.
机译:钾通道是跨膜的四聚体蛋白,可为K +跨细胞膜的传导提供选择性的孔。钾离子通道的主要生理功能之一是将K +离子有效且选择性地通过膜转运至细胞。离子选择性的经典观点在一个历史的视角下进行了总结,并与分子动力学(MD)模拟,基于KcsA磷脂膜的晶体结构进行的自由能扰动(FEP)进行了对比。结果表明,通过提供适当(固定)腔尺寸的结合位点,KcsA通道不会选择K +离子。而是,对K +的选择性直接来自配体在结合位点配位的阳离子的固有局部物理性质,并且是由骨架羰基对称排列的孔的坚固特征。进一步的分析表明,吸引离子-配体(有利于较小的阳离子)和排斥性配体-配体相互作用(有利于较大的阳离子)之间的相互作用是控制柔性蛋白质结合位点中Na + / K +选择性的基本元素。因为配位离子的配体的数量和类型直接调节这种局部相互作用,所以尽管具有显着的构象柔韧性,但仍提供了一种有效的分子机制来实现并维持蛋白质结合位点的高选择性。 (c)2006 Elsevier B.V.保留所有权利。

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