CaltechAUTHORS
  A Caltech Library Service

Connection between Oligomeric State and Gating Characteristics of Mechanosensitive Ion Channels

Haselwandter, Christoph A. and Phillips, Rob (2013) Connection between Oligomeric State and Gating Characteristics of Mechanosensitive Ion Channels. PLoS Computational Biology, 9 (5). Art. No. e1003055. ISSN 1553-734X. PMCID PMC3656111. doi:10.1371/journal.pcbi.1003055. https://resolver.caltech.edu/CaltechAUTHORS:20130718-104555723

[img]
Preview
PDF - Published Version
Creative Commons Attribution.

2MB
[img] Postscript (Figure S1) - Supplemental Material
Creative Commons Attribution.

1MB
[img] Postscript (Figure S2) - Supplemental Material
Creative Commons Attribution.

1MB
[img] Postscript (Figure S3) - Supplemental Material
Creative Commons Attribution.

1MB
[img] Postscript (Figure S4) - Supplemental Material
Creative Commons Attribution.

1MB

Use this Persistent URL to link to this item: https://resolver.caltech.edu/CaltechAUTHORS:20130718-104555723

Abstract

The mechanosensitive channel of large conductance (MscL) is capable of transducing mechanical stimuli such as membrane tension into an electrochemical response. MscL provides a widely-studied model system for mechanotransduction and, more generally, for how bilayer mechanical properties regulate protein conformational changes. Much effort has been expended on the detailed experimental characterization of the molecular structure and biological function of MscL. However, despite its central significance, even basic issues such as the physiologically relevant oligomeric states and molecular structures of MscL remain a matter of debate. In particular, tetrameric, pentameric, and hexameric oligomeric states of MscL have been proposed, together with a range of detailed molecular structures of MscL in the closed and open channel states. Previous theoretical work has shown that the basic phenomenology of MscL gating can be understood using an elastic model describing the energetic cost of the thickness deformations induced by MscL in the surrounding lipid bilayer. Here, we generalize this elastic model to account for the proposed oligomeric states and hydrophobic shapes of MscL. We find that the oligomeric state and hydrophobic shape of MscL are reflected in the energetic cost of lipid bilayer deformations. We make quantitative predictions pertaining to the gating characteristics associated with various structural models of MscL and, in particular, show that different oligomeric states and hydrophobic shapes of MscL yield distinct membrane contributions to the gating energy and gating tension. Thus, the functional properties of MscL provide a signature of the oligomeric state and hydrophobic shape of MscL. Our results suggest that, in addition to the hydrophobic mismatch between membrane proteins and the surrounding lipid bilayer, the symmetry and shape of the hydrophobic surfaces of membrane proteins play an important role in the regulation of protein function by bilayer membranes.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1371/journal.pcbi.1003055 DOIArticle
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3656111/PubMed CentralArticle
ORCID:
AuthorORCID
Phillips, Rob0000-0003-3082-2809
Additional Information:© 2013 Haselwandter, Phillips. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Received October 24, 2012; Accepted March 8, 2013; Published May 16, 2013. Editor: Alexandre V. Morozov, Rutgers University, United States of America. Funding: This work was supported at USC by the National Science Foundation through NSF award number DMR-1206332 (http://www.nsf.gov/) and at Caltech by a Collaborative Innovation Award of the Howard Hughes Medical Institute (http://www.hhmi.org/), and the National Institutes of Health through NIH award number R01 GM084211 and the Director’s Pioneer Award (http://www.nih.gov/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. We thank W. S. Klug, M. Lindén, D. C. Rees, and N. S. Wingreen for helpful comments. Author Contributions: Conceived and designed the experiments: CAH RP. Performed the experiments: CAH. Analyzed the data: CAH RP. Wrote the paper: CAH RP.
Funders:
Funding AgencyGrant Number
NSFDMR-1206332
Howard Hughes Medical Institute (HHMI)UNSPECIFIED
NIHR01 GM084211
Issue or Number:5
PubMed Central ID:PMC3656111
DOI:10.1371/journal.pcbi.1003055
Record Number:CaltechAUTHORS:20130718-104555723
Persistent URL:https://resolver.caltech.edu/CaltechAUTHORS:20130718-104555723
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:39443
Collection:CaltechAUTHORS
Deposited By: Tony Diaz
Deposited On:22 Jul 2013 23:13
Last Modified:09 Nov 2021 23:44

Repository Staff Only: item control page