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PMID: 15339798 Published · ppublish English Comparative Study Evaluation Study Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

Molecular dynamics study of gating in the mechanosensitive channel of small conductance MscS.

Biophysical journal ·Vol. 87 ·No. 5 ·2004-11-00 ·Pages 3050-65

Sotomayor M, Schulten K

Abstract

Mechanosensitive channels are a class of ubiquitous membrane proteins gated by mechanical strain in the cellular membrane. MscS, the mechanosensitive channel of small conductance, is found in the inner membrane of Escherichia coli and its crystallographic structure in an open form has been recently solved. By means of molecular dynamics simulations we studied the stability of the channel conformation suggested by crystallography in a fully solvated lipid (POPC) bilayer, the combined system encompassing 224,340 atoms. When restraining the backbone of the protein, the channel remained in the open form and the simulation revealed intermittent permeation of water molecules through the channel. Abolishing the restraints under constant pressure conditions led to spontaneous closure of the transmembrane channel, whereas abolishing the restraints when surface tension (20 dyn/cm) was applied led to channel widening. The large balloon-shaped cytoplasmic domain of MscS exhibited spontaneous diffusion of ions through its side openings. Interaction between the transmembrane domain and the cytoplasmic domain of MscS was observed and involved formation of salt bridges between residues Asp62 and Arg128; this interaction may be essential for the gating of MscS. K+ and Cl- ions showed distinctively different distributions in and around the channel.

MeSH Terms
Computer Simulation Electric Conductivity Escherichia coli Proteins/chemistry Ion Channel Gating Ion Channels/chemistry Kinetics Lipid Bilayers/chemistry Mechanotransduction, Cellular Membrane Fluidity Models, Chemical Models, Molecular Motion Phosphatidylcholines/chemistry Physical Stimulation/methods Porosity Protein Conformation Stress, Mechanical Surface Tension Water/chemistry
Chemicals
Escherichia coli Proteins Ion Channels Lipid Bilayers MscS protein, E coli Phosphatidylcholines Water 1-palmitoyl-2-oleoylphosphatidylcholine
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Sotomayor Marcos
Department of Physics, University of Illinois at Urbana-Champaign, and Beckman Institute for Advanced Science and Technology, Urbana, Illinois.
Schulten Klaus
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Article Info
Journal
Biophysical journal
Abbr.
Biophys J
ISSN
0006-3495
DOI
10.1529/biophysj.104.046045
Published
2004-11-00
Epub
2004-00-31
Pages
3050-65
Language
English
Region
United States
NLM ID
0370626
PMCID
PMC1304777
Subset
IM
Grants
NCRR NIH HHS · P41 RR005969 · United States
NIGMS NIH HHS · R01 GM067887 · United States
External Links
PubMed source DOI: 10.1529/biophysj.104.046045 PMC Full Text View journal details
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