Gating of MscL studied by steered molecular dynamics.
Steered molecular dynamics simulations of the mechanosensitive channel of large conductance, MscL, were used to investigate how forces arising from membrane tension induce gating of the channel. A homology model of the closed form of MscL from Escherichia coli was subjected to external forces of 35-70 pN applied to residues near the membrane-water interface. The magnitude and location of these forces corresponded to those determined from the lateral pressure profile computed from a lipid bilayer simulation. A fully expanded state was obtained on the 10-ns timescale that revealed the mechanism for transducing membrane forces into channel opening. The expanded state agrees well with proposed models of MscL gating, in that it entails an irislike expansion of the pore accompanied by tilting of the transmembrane helices. The channel was most easily opened when force was applied predominantly on the cytoplasmic side of MscL. Comparison of simulations in which gating progressed to varying degrees identified residues that pose steric hindrance to channel opening.
D001665:Binding Sites; D003198:Computer Simulation; D029968:Escherichia coli Proteins / Q000737:chemistry* / Q000502:physiology*; D015640:Ion Channel Gating / Q000502:physiology*; D007473:Ion Channels / Q000737:chemistry* / Q000502:physiology*; D008051:Lipid Bilayers / Q000737:chemistry* / Q000378:metabolism*; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D008560:Membrane Fluidity; D008954:Models, Biological; D008958:Models, Molecular; D009038:Motion; D010714:Phosphatidylethanolamines / Q000737:chemistry / Q000378:metabolism; D016062:Porosity; D011485:Protein Binding; D011487:Protein Conformation; D013314:Stress, Mechanical
D029968:Escherichia coli Proteins; D007473:Ion Channels; D008051:Lipid Bilayers; C086596:MscL protein, E coli; D010714:Phosphatidylethanolamines; C007445:1,2-dilauroylphosphatidylethanolamine