Structural mechanism of C-type inactivation in K(+) channels.
Structural mechanism of C-type inactivation in K(+) channels.
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K+通道选择性过滤器的导电和非导电形式之间的相互转换是各种门控事件的基础，从闪烁转变(μS)到C型失活(MS-S)。在这里，我们报道了K+通道KCSA在开放-失活构象中的晶体结构，并研究了在一系列部分开放构象中“捕获”的通道在选择性过滤器处的C型失活门控机制。确定了5个具有开口的整形等级，从闭合KCSA中的12？(T112处的Cα-Cα距离)到完全打开时的32？结果表明，栅极开度与选择性滤膜的构象和离子占有率之间存在显着的相关性。我们表明，逐渐的过滤主干重定向首先导致S2离子结合位点的丢失，随后是S3结合位点的丢失，推测这可能会破坏离子传导。这些结构提示了K+通道C型失活的分子基础。
Interconversion between conductive and non-conductive forms of the K+ channel selectivity filter underlies a variety of gating events, from flicker transitions (μs) to C-type inactivation (ms-s). Here, we report the crystal structure of the K+ channel KcsA in its Open-Inactivated conformation and investigate the mechanism of C-type inactivation gating at the selectivity filter from channels “trapped” in a series of partially open conformations. Five conformer classes were identified with openings ranging, from 12 Å in closed KcsA (Cα-Cα distances at T112) to 32 Å when fully open. They revealed a remarkable correlation between the degree of gate opening and the conformation and ion occupancy of the selectivity filter. We show that a gradual filter backbone reorientation leads first, to a loss of the S2 ion binding site and a subsequent loss of the S3 binding site, presumably abrogating ion conduction. These structures suggest a molecular basis for C-type inactivation in K+ channels.
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