The Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia.
Cell. 2010 Jun 11;141(6):1018-29. doi: 10.1016/j.cell.2010.05.003.
Potassium channels embedded in cell membranes employ gates to regulate K+ current. While a specific constriction in the permeation pathway has historically been implicated in gating, recent reports suggest that the signature ion selectivity filter located in the outer membrane leaflet may be equally important. Inwardly rectifying K+ channels also control the directionality of flow, using intracellular polyamines to stem ion efflux by a valve-like action. This study presents crystallographic evidence of interdependent gates in the conduction pathway and reveals the mechanism of polyamine block. Reorientation of the intracellular domains, concomitant with activation, instigates polyamine release from intracellular binding sites to block the permeation pathway. Conformational adjustments of the slide helices, achieved by rotation of the cytoplasmic assembly relative to the pore, are directly correlated to the ion configuration in the selectivity filter. Ion redistribution occurs irrespective of the constriction, suggesting a more expansive role of the selectivity filter in gating than previously appreciated.
细胞膜中的钾通道利用门控来调节 K+ 电流。虽然渗透途径中的特定狭窄部位历来与门控有关，但最近的报告表明，位于外膜叶的特征性离子选择性滤器可能同样重要。内向整流钾通道也通过类似阀的作用控制离子流出的方向，利用细胞内多胺来阻止离子外流。本研究提供了传导途径中相互依存的门控的晶体结构证据，并揭示了多胺阻断的机制。伴随激活的细胞内结构域的重定向，促使多胺从细胞内结合位点释放，从而阻断渗透途径。通过细胞质组件相对于孔的旋转实现滑动螺旋的构象调整，与选择性过滤器中的离子构型直接相关。离子再分配的发生与狭窄无关，这表明选择性过滤器在门控中的作用比以前认为的更为广泛。
