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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| Format: | Online |
| Language: | English |
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The Rockefeller University Press
2011
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| Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3135322/ |
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pubmed-31353222012-01-01 The pathway and spatial scale for MscS inactivation Kamaraju, Kishore Belyy, Vladislav Rowe, Ian Anishkin, Andriy Sukharev, Sergei 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 nm2, 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/). |
| repository_type |
Open Access Journal |
| institution_category |
Foreign Institution |
| institution |
US National Center for Biotechnology Information |
| building |
NCBI PubMed |
| collection |
Online Access |
| language |
English |
| format |
Online |
| author |
Kamaraju, Kishore Belyy, Vladislav Rowe, Ian Anishkin, Andriy Sukharev, Sergei |
| spellingShingle |
Kamaraju, Kishore Belyy, Vladislav Rowe, Ian Anishkin, Andriy Sukharev, Sergei The pathway and spatial scale for MscS inactivation |
| author_facet |
Kamaraju, Kishore Belyy, Vladislav Rowe, Ian Anishkin, Andriy Sukharev, Sergei |
| author_sort |
Kamaraju, Kishore |
| title |
The pathway and spatial scale for MscS inactivation |
| title_short |
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_sort |
pathway and spatial scale for mscs inactivation |
| 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 nm2, 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. |
| publisher |
The Rockefeller University Press |
| publishDate |
2011 |
| url |
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3135322/ |
| _version_ |
1611465225616228352 |