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PMID: 20208543 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

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

Nature structural & molecular biology ·Vol. 17 ·No. 4 ·2010-04-00 ·Pages 451-8

Belyy V, Anishkin A, Kamaraju K, Liu N, Sukharev S

Abstract

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.

MeSH Terms
Escherichia coli/physiology Escherichia coli Proteins/chemistry,physiology Ion Channels/chemistry,physiology Models, Molecular Molecular Dynamics Simulation Protein Conformation
Chemicals
Escherichia coli Proteins Ion Channels MscS protein, E coli
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Belyy Vladislav
Department of Biology, University of Maryland College Park, College Park, Maryland, USA.
Anishkin Andriy
Kamaraju Kishore
Liu Naili
Sukharev Sergei
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Article Info
Journal
Nature structural & molecular biology
Abbr.
Nat Struct Mol Biol
ISSN
1545-9985
DOI
10.1038/nsmb.1775
Published
2010-04-00
Epub
2010-00-07
Pages
451-8
Language
English
Region
United States
NLM ID
101186374
Subset
IM
Grants
Howard Hughes Medical Institute · United States
External Links
PubMed source DOI: 10.1038/nsmb.1775 View journal details
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