title: Mechanosensitive membrane channels in action.
abstract: The tension-driven gating process of MscL from Mycobacterium tuberculosis, Tb-MscL, has been addressed at near-atomic detail using coarse-grained molecular dynamics simulations. To perform the simulations, a novel coarse-grained peptide model based on a thermodynamic parameterization of the amino-acid side chains has been applied. Both the wild-type Tb-MscL and its gain-of-function mutant V21D embedded in a solvated lipid bilayer have been studied. To mimic hypoosmotic shock conditions, simulations were performed at increasing levels of membrane tension approaching the rupture threshold of the lipid bilayer. Both the wild-type and the mutant channel are found to undergo significant conformational changes in accordance with an irislike expansion mechanism, reaching a conducting state on a microsecond timescale. The most pronounced expansion of the pore has been observed for the V21D mutant, which is consistent with the experimentally shown gain-of-function phenotype of the V21D mutant.
authors.affiliation: Zernike Institute for Advanced Materials, Department of Applied Physics, University of Groningen, Nijenborgh, Groningen, The Netherlands.
authors.forename: Serge
authors.initials: S
authors.lastname: Yefimov
authors.forename: Erik
authors.initials: E
authors.lastname: van der Giessen
authors.forename: Patrick R
authors.initials: PR
authors.lastname: Onck
authors.forename: Siewert J
authors.initials: SJ
authors.lastname: Marrink
mesh_terms: D002462:Cell Membrane / Q000737:chemistry / Q000502:physiology*; 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; D008465:Mechanoreceptors / Q000502:physiology*; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D008954:Models, Biological; D008956:Models, Chemical; D008958:Models, Molecular; D013314:Stress, Mechanical
chemical_list: D029968:Escherichia coli Proteins; D007473:Ion Channels; D008051:Lipid Bilayers; C086596:MscL protein, E coli