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PMID: 16513774 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, Non-P.H.S.

Electrostatic properties of the mechanosensitive channel of small conductance MscS.

Biophysical journal ·Vol. 90 ·No. 10 ·2006-05-15 ·Pages 3496-510

Sotomayor M, van der Straaten TA, Ravaioli U, Schulten K

Abstract

The mechanosensitive channel of small conductance (MscS) belongs to a family of membrane proteins that are gated in response to changes in membrane tension, thereby protecting the cell from hypo-osmotic shock. Here we report on passive ion transport simulations of MscS in a POPC bilayer using a coarse-grained particle-based description based on the Boltzmann transport Monte Carlo method. Single channel current-voltage curves are computed over hundreds of nanoseconds for channel conformations derived from all-atom molecular dynamics simulations reaching an overall simulation time of over 5 micros. Channel conformations similar to that of the crystal structure exhibit low conductance, whereas conformations reached after opening the channel by means of steered molecular dynamics simulations match experimentally determined conductances. However, while experiments indicate a slight preference for anionic currents, the simulated channel strongly selects anions over cations and the direction of rectification at high voltages is opposite to what is observed in experiments. Three-dimensional maps of time-averaged ion distribution and equilibrium occupancy profiles constructed from trajectory data indicate separation of anions and cations inside and in the immediate vicinity of the large cytoplasmic domain of MscS, in accordance with earlier molecular dynamics simulations. This separation arises from the distribution of ionizable residues of MscS and suggests a specific, yet unknown, functional purpose.

MeSH Terms
Cell Membrane/chemistry Computer Simulation Electric Conductivity Escherichia coli Proteins/chemistry,ultrastructure Ion Channel Gating Ion Channels/chemistry,ultrastructure Mechanotransduction, Cellular Membrane Potentials Models, Chemical Models, Molecular Protein Conformation Static Electricity Stress, Mechanical
Chemicals
Escherichia coli Proteins Ion Channels MscS protein, E coli
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Sotomayor Marcos
Department of Physics, Beckman Institute for Advanced Science and Technology, University of Illinois at Urbana-Champaign, USA.
van der Straaten Trudy A
Ravaioli Umberto
Schulten Klaus
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Article Info
Journal
Biophysical journal
Abbr.
Biophys J
ISSN
0006-3495
DOI
10.1529/biophysj.105.080069
Published
2006-05-15
Epub
2006-00-02
Pages
3496-510
Language
English
Region
United States
NLM ID
0370626
PMCID
PMC1440732
Subset
IM
Grants
NIGMS NIH HHS · R01 GM073655 · United States
NCRR NIH HHS · P41 RR005969 · United States
NIGMS NIH HHS · R01 GM067887 · United States
NIGMS NIH HHS · 1 RO1 GM067887 · United States
NIGMS NIH HHS · R01-GM073655 · United States
NCRR NIH HHS · P41 RR05969 · United States
External Links
PubMed source DOI: 10.1529/biophysj.105.080069 PMC Full Text View journal details
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