The tension-transmitting 'clutch' in the mechanosensitive channel MscS

被引：62

作者：

Belyy, Vladislav ^{[1
]}

Anishkin, Andriy ^{[1
]}

Kamaraju, Kishore ^{[1
]}

Liu, Naili ^{[1
]}

Sukharev, Sergei ^{[1
]}

机构：

[1] Univ Maryland, Dept Biol, College Pk, MD 20742 USA

来源：

NATURE STRUCTURAL & MOLECULAR BIOLOGY | 2010年 / 17卷 / 04期

基金：

美国国家卫生研究院;

关键词：

ESCHERICHIA-COLI MSCS; MOLECULAR-DYNAMICS; SMALL-CONDUCTANCE; MEMBRANE; PROTEINS; WATER; MUTAGENESIS; ACTIVATION; TRANSITION; MECHANISM;

D O I：

10.1038/nsmb.1775

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：

Under prolonged stimulation, the mechanosensitive channel MscS of Escherichia coli enters a tension-insensitive inactivated state. We transformed the delipidated crystal structure and restored the link between lipid-facing TM1 and TM2 and gate-forming TM3 helices. Joining the conserved Phe68 of TM2 with Leu111 of TM1, this buried contact mediated opening in steered molecular dynamics simulations with forces applied to the peripheral helices. Both F68S and L111S substitutions produced severe loss-of-function phenotypes in vivo by increasing the inactivation rate and promoting unusual 'silent' inactivation from the resting state. F68S also suppressed the noninactivating phenotype of G113A. The L111C cysteine buried in the TM2-TM3 crevice was accessible to methanethiosulfonate-ethyltrimethylammonium (MTSET) only in the inactivated state, which was stabilized upon modification by a positive charge. The restored interhelical contact thus is critically involved in force transmission from the lipid-facing helices to the gate, and inactivation appears to be a result of TM2-TM3 uncoupling.

引用

页码：451 / U92

页数：9

共 37 条

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