The nonconducting W434F mutant adopts upon membrane depolarization an inactivated-like state that differs from wild-type Shaker-IR potassium channels.
The nonconducting W434F mutant adopts upon membrane depolarization an inactivated-like state that differs from wild-type Shaker-IR potassium channels.
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DOI：
10.1126/sciadv.abn1731
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发表时间：
2022-09-16
期刊：
影响因子：
13.6
通讯作者：
中科院分区：
文献类型：
--
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电压门控K+通道通过调节其激活门（AG）的传导状态来介导K+穿过细胞膜的流动。几个KV通道显示缓慢的C型失活，这是一个过程，使其选择性过滤器（SF）变得不导电或不导电。有人提出，在快速失活去除的Shaker-IR通道中，W 434 F突变表位C型失活状态，因为它在功能上加速了这一过程。通过引入另一个阻止AG闭合的孔突变P475 D，我们发现了一种方法，当W 434 F突变体SF从其失活状态恢复时，在超极化膜电位下记录Shaker-IR-W 434 F-P475 D突变体的离子电流。这种W 434 F导电状态失去了其高K+对Na+的选择性，甚至NMDG+也可以渗透，这在野生型SF中没有观察到。这表明，至少在失活恢复期间，W 434 F突变体SF转变为加宽的非阳离子特异性构象。快速失活的W 434 F突变体使Shaker-IR K+通道稳定在非生理相关的关闭或失活状态。
Voltage-gated K+ (Kv) channels mediate the flow of K+ across the cell membrane by regulating the conductive state of their activation gate (AG). Several Kv channels display slow C-type inactivation, a process whereby their selectivity filter (SF) becomes less or nonconductive. It has been proposed that, in the fast inactivation-removed Shaker-IR channel, the W434F mutation epitomizes the C-type inactivated state because it functionally accelerates this process. By introducing another pore mutation that prevents AG closure, P475D, we found a way to record ionic currents of the Shaker-IR-W434F-P475D mutant at hyperpolarized membrane potentials as the W434F-mutant SF recovers from its inactivated state. This W434F conductive state lost its high K+ over Na+ selectivity, and even NMDG+ can permeate, features not observed in a wild-type SF. This indicates that, at least during recovery from inactivation, the W434F-mutant SF transitions to a widened and noncationic specific conformation. The fast-inactivating W434F mutant stabilizes the Shaker-IR K+ channel in a nonphysiological relevant shut or inactivated state.
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影响因子：
56.9
作者：
Doyle, DA;Cabral, JM;MacKinnon, R
通讯作者：
MacKinnon, R
DOI：
10.1085/jgp.200609638
发表时间：
2006-11
期刊：
The Journal of general physiology
影响因子：
--
作者：
Blunck R;Cordero-Morales JF;Cuello LG;Perozo E;Bezanilla F
通讯作者：
Bezanilla F
DOI：
10.1107/s0907444904019158
发表时间：
2004-12-01
影响因子：
2.2
作者：
Emsley, P;Cowtan, K
通讯作者：
Cowtan, K
影响因子：
4.8
作者：
Labro, AJ;Raes, AL;Snyders, DJ
通讯作者：
Snyders, DJ
影响因子：
16.2
作者：
KIRSCH, GE;SHIEH, CC;BROWN, AM
通讯作者：
BROWN, AM