Conformational changes and gating at the selectivity filter of potassium channels
Conformational changes and gating at the selectivity filter of potassium channels
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DOI：
10.1021/ja801792g
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发表时间：
2008-07-23
影响因子：
15
通讯作者：
Parrinello, Michele
中科院分区：
文献类型：
--
作者：
Domene, Carmen;Klein, Michael L.;Parrinello, Michele
离子和水穿过细胞膜的转移是许多生命过程的先决条件。K+通道是一个复杂的膜蛋白家族，K+可以选择性地通过它。关于钾离子通道的开放和关闭以及传导和非传导状态相关的构象变化的性质一直存在争议。这些变化取决于膜电位，K+浓度梯度，和跨膜螺旋和相关残基的大规模运动。实验还表明，选择性过滤器中的局部结构变化可能充当被称为C型失活的主导门。在这里，我们提出了一个广泛的计算研究KirBac，支持存在一个物理门或收缩的选择性过滤器（SF）的K+通道。我们的计算确定了一个新的选择性过滤器结构，这可能与C型失活。具体而言，组成过滤器的四条肽链采用了一种不寻常的结构，其中它们的二面角在左手和右手拉氏角之间交替，这也证明了需要在K+选择性过滤器中保护甘氨酸，因为它是唯一能够发挥这种双功能作用的残基。
The translocation of ions and water across cell membranes is a prerequisite for many of life's processes. K+ channels are a diverse family of integral membrane proteins through which K+ can pass selectively. There is an ongoing debate about the nature of conformational changes associated with the opening and closing and conductive and nonconductive states of potassium (K+) channels. These changes depend on the membrane potential, the K+ concentration gradient, and large scale motions of transmembrane helices and associated residues. Experiments also suggest that local structural changes in the selectivity filter may act as the dominant gate referred to as C-type inactivation. Herein we present an extensive computational study on KirBac, which supports the existence of a physical gate or constriction in the selectivity filter (SF) of K+ channels. Our computations identify a new selectivity filter structure, which is likely associated with C-type inactivation. Specifically, the four peptide chains that comprise the filter adopt an unusual structure in which their dihedrals alternate between left- and right-handed Ramachandran angles, which also justifies the need for conservation of glycine in the K+ selectivity filter, since it is the only residue able to play this bifunctional role.