title: Molecular dynamics study of gating in the mechanosensitive channel of small conductance MscS.
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.
authors.affiliation: Department of Physics, University of Illinois at Urbana-Champaign, and Beckman Institute for Advanced Science and Technology, Urbana, Illinois.
authors.forename: Marcos
authors.initials: M
authors.lastname: Sotomayor
authors.forename: Klaus
authors.initials: K
authors.lastname: Schulten
mesh_terms: D003198:Computer Simulation; D004553:Electric Conductivity; D029968:Escherichia coli Proteins / Q000737:chemistry*; D015640:Ion Channel Gating; D007473:Ion Channels / Q000737:chemistry*; D007700:Kinetics; D008051:Lipid Bilayers / Q000737:chemistry*; D040542:Mechanotransduction, Cellular; D008560:Membrane Fluidity; D008956:Models, Chemical; D008958:Models, Molecular; D009038:Motion; D010713:Phosphatidylcholines / Q000737:chemistry*; D010812:Physical Stimulation / Q000379:methods; D016062:Porosity; D011487:Protein Conformation; D013314:Stress, Mechanical; D013500:Surface Tension; D014867:Water / Q000737:chemistry
chemical_list: D029968:Escherichia coli Proteins; D007473:Ion Channels; D008051:Lipid Bilayers; C469542:MscS protein, E coli; D010713:Phosphatidylcholines; D014867:Water; C028694:1-palmitoyl-2-oleoylphosphatidylcholine