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The pathway and spatial scale for MscS inactivation

The mechanosensitive channel of small conductance (MscS) is a bacterial tension-driven osmolyte release valve with homologues in many walled eukaryotic organisms. When stimulated by steps of tension in excised patches, Escherichia coli MscS exhibits transient opening followed by reversible adaptatio...

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Autores principales: Kamaraju, Kishore, Belyy, Vladislav, Rowe, Ian, Anishkin, Andriy, Sukharev, Sergei
Formato: Online Artículo Texto
Lenguaje:English
Publicado: The Rockefeller University Press 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3135322/
https://www.ncbi.nlm.nih.gov/pubmed/21670207
http://dx.doi.org/10.1085/jgp.201110606
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author Kamaraju, Kishore
Belyy, Vladislav
Rowe, Ian
Anishkin, Andriy
Sukharev, Sergei
author_facet Kamaraju, Kishore
Belyy, Vladislav
Rowe, Ian
Anishkin, Andriy
Sukharev, Sergei
author_sort Kamaraju, Kishore
collection PubMed
description The mechanosensitive channel of small conductance (MscS) is a bacterial tension-driven osmolyte release valve with homologues in many walled eukaryotic organisms. When stimulated by steps of tension in excised patches, Escherichia coli MscS exhibits transient opening followed by reversible adaptation and then complete inactivation. Here, we study properties of the inactivation transition, which renders MscS nonconductive and tension insensitive. Using special pressure protocols we demonstrate that adaptation and inactivation are sequential processes with opposite tension dependencies. In contrast to many eukaryotic channels, which inactivate from the open state, MscS inactivates primarily from the closed state because full openings by preconditioning pulses do not influence the degree of inactivation, and saturating tensions keeping channels open prevent inactivation. The easily opened A98S mutant lacks inactivation completely, whereas the L111S mutant with a right-shifted activation curve inactivates silently before reaching the threshold for opening. This suggests that opening and inactivation are two independent tension-driven pathways, both starting from the closed state. Analysis of tension dependencies for inactivation and recovery rates estimated the in-plane expansion (ΔA) associated with inactivation as 8.5 nm(2), which is about half of the area change for opening. Given that the interhelical contact between the outer TM1–TM2 pairs and the core TM3s is the force-transmitting path from the periphery to the gate, the determined ΔA now can be used as a constraining parameter for the models of the inactivated state in which the lipid-facing TM1–TM2 pairs are displaced and uncoupled from the gate.
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spelling pubmed-31353222012-01-01 The pathway and spatial scale for MscS inactivation Kamaraju, Kishore Belyy, Vladislav Rowe, Ian Anishkin, Andriy Sukharev, Sergei J Gen Physiol Article The mechanosensitive channel of small conductance (MscS) is a bacterial tension-driven osmolyte release valve with homologues in many walled eukaryotic organisms. When stimulated by steps of tension in excised patches, Escherichia coli MscS exhibits transient opening followed by reversible adaptation and then complete inactivation. Here, we study properties of the inactivation transition, which renders MscS nonconductive and tension insensitive. Using special pressure protocols we demonstrate that adaptation and inactivation are sequential processes with opposite tension dependencies. In contrast to many eukaryotic channels, which inactivate from the open state, MscS inactivates primarily from the closed state because full openings by preconditioning pulses do not influence the degree of inactivation, and saturating tensions keeping channels open prevent inactivation. The easily opened A98S mutant lacks inactivation completely, whereas the L111S mutant with a right-shifted activation curve inactivates silently before reaching the threshold for opening. This suggests that opening and inactivation are two independent tension-driven pathways, both starting from the closed state. Analysis of tension dependencies for inactivation and recovery rates estimated the in-plane expansion (ΔA) associated with inactivation as 8.5 nm(2), which is about half of the area change for opening. Given that the interhelical contact between the outer TM1–TM2 pairs and the core TM3s is the force-transmitting path from the periphery to the gate, the determined ΔA now can be used as a constraining parameter for the models of the inactivated state in which the lipid-facing TM1–TM2 pairs are displaced and uncoupled from the gate. The Rockefeller University Press 2011-07 /pmc/articles/PMC3135322/ /pubmed/21670207 http://dx.doi.org/10.1085/jgp.201110606 Text en © 2011 Kamaraju et al. This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).
spellingShingle Article
Kamaraju, Kishore
Belyy, Vladislav
Rowe, Ian
Anishkin, Andriy
Sukharev, Sergei
The pathway and spatial scale for MscS inactivation
title The pathway and spatial scale for MscS inactivation
title_full The pathway and spatial scale for MscS inactivation
title_fullStr The pathway and spatial scale for MscS inactivation
title_full_unstemmed The pathway and spatial scale for MscS inactivation
title_short The pathway and spatial scale for MscS inactivation
title_sort pathway and spatial scale for mscs inactivation
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3135322/
https://www.ncbi.nlm.nih.gov/pubmed/21670207
http://dx.doi.org/10.1085/jgp.201110606
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