Coupling of activation and inactivation gate in a K+-channel: potassium and ligand sensitivity

被引:78
作者
Ader, Christian [1 ]
Schneider, Robert [2 ]
Hornig, Soenke [3 ]
Velisetty, Phanindra [3 ]
Vardanyan, Vitya [3 ]
Giller, Karin [2 ]
Ohmert, Iris [3 ]
Becker, Stefan [2 ]
Pongs, Olaf [3 ]
Baldus, Marc [1 ]
机构
[1] Univ Utrecht, Bijvoet Ctr Biomol Res, NL-3584 CH Utrecht, Netherlands
[2] Max Planck Inst Biophys Chem, Dept NMR Based Struct Biol, D-37077 Gottingen, Germany
[3] Univ Hosp Hamburg Eppendorf, Ctr Mol Neurobiol, Inst Neural Signaltransduct, Hamburg, Germany
关键词
ion-channel gating; K+-channel; membrane protein; pH sensor; solid-state NMR; SOLID-STATE NMR; C-TYPE-INACTIVATION; INDUCED CONFORMATIONAL-CHANGES; STREPTOMYCES-LIVIDANS; SELECTIVITY FILTER; STRUCTURAL REARRANGEMENTS; QUANTITATIVE DESCRIPTION; MOLECULAR-MECHANISM; SLOW INACTIVATION; KCSA;
D O I
10.1038/emboj.2009.218
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Potassium (K+)-channel gating is choreographed by a complex interplay between external stimuli, K+ concentration and lipidic environment. We combined solid-state NMR and electrophysiological experiments on a chimeric KcsA-Kv1.3 channel to delineate K+, pH and blocker effects on channel structure and function in a membrane setting. Our data show that pH-induced activation is correlated with protonation of glutamate residues at or near the activation gate. Moreover, K+ and channel blockers distinctly affect the open probability of both the inactivation gate comprising the selectivity filter of the channel and the activation gate. The results indicate that the two gates are coupled and that effects of the permeant K+ ion on the inactivation gate modulate activation-gate opening. Our data suggest a mechanism for controlling coordinated and sequential opening and closing of activation and inactivation gates in the K+-channel pore. The EMBO Journal (2009) 28, 2825-2834. doi: 10.1038/emboj.2009.218; Published online 6 August 2009
引用
收藏
页码:2825 / 2834
页数:10
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