title: The role of MscL amphipathic N terminus indicates a blueprint for bilayer-mediated gating of mechanosensitive channels.
abstract: The bacterial mechanosensitive channel MscL gates in response to membrane tension as a result of mechanical force transmitted directly to the channel from the lipid bilayer. MscL represents an excellent model system to study the basic biophysical principles of mechanosensory transduction. However, understanding of the essential structural components that transduce bilayer tension into channel gating remains incomplete. Here using multiple experimental and computational approaches, we demonstrate that the amphipathic N-terminal helix of MscL acts as a crucial structural element during tension-induced gating, both stabilizing the closed state and coupling the channel to the membrane. We propose that this may also represent a common principle in the gating cycle of unrelated mechanosensitive ion channels, allowing the coupling of channel conformation to membrane dynamics.
authors.affiliation: Division of Molecular Cardiology and Biophysics, Victor Chang Cardiac Research Institute, Darlinghurst, New South Wales 2010, Australia.|St Vincent's Clinical School, Faculty of Medicine, University of New South Wales, Darlinghurst, New South Wales 2010, Australia.
authors.forename: Navid
authors.identifier: 0000-0001-7040-0710
authors.initials: N
authors.lastname: Bavi
authors.affiliation: Department of Biochemistry and Molecular Biology, Institute for Biophysical Dynamics, University of Chicago, Chicago, Illinois 60637, USA.
authors.forename: D Marien
authors.initials: DM
authors.lastname: Cortes
authors.affiliation: Division of Molecular Cardiology and Biophysics, Victor Chang Cardiac Research Institute, Darlinghurst, New South Wales 2010, Australia.|St Vincent's Clinical School, Faculty of Medicine, University of New South Wales, Darlinghurst, New South Wales 2010, Australia.
authors.forename: Charles D
authors.initials: CD
authors.lastname: Cox
authors.affiliation: Division of Molecular Cardiology and Biophysics, Victor Chang Cardiac Research Institute, Darlinghurst, New South Wales 2010, Australia.
authors.forename: Paul R
authors.initials: PR
authors.lastname: Rohde
authors.affiliation: Department of Pharmacology, University of Western Australia, Nedlands, Western Australia 6009, Australia.
authors.forename: Weihong
authors.initials: W
authors.lastname: Liu
authors.affiliation: FB Biologie, University of Kaiserslautern, Kaiserslautern D-67663, Germany.
authors.forename: Joachim W
authors.initials: JW
authors.lastname: Deitmer
authors.affiliation: Division of Molecular Cardiology and Biophysics, Victor Chang Cardiac Research Institute, Darlinghurst, New South Wales 2010, Australia.|Institute for Nanoscience and Nanotechnology, Sharif University of Technology, Tehran 1458889694, Iran.
authors.forename: Omid
authors.initials: O
authors.lastname: Bavi
authors.affiliation: Division of Chemistry and Chemical Engineering, Howard Hughes Medical Institute, California Institute of Technology, Pasadena, California 91125, USA.
authors.forename: Pavel
authors.initials: P
authors.lastname: Strop
authors.affiliation: Division of Molecular Cardiology and Biophysics, Victor Chang Cardiac Research Institute, Darlinghurst, New South Wales 2010, Australia.|St Vincent's Clinical School, Faculty of Medicine, University of New South Wales, Darlinghurst, New South Wales 2010, Australia.
authors.forename: Adam P
authors.initials: AP
authors.lastname: Hill
authors.affiliation: Division of Chemistry and Chemical Engineering, Howard Hughes Medical Institute, California Institute of Technology, Pasadena, California 91125, USA.
authors.forename: Douglas
authors.initials: D
authors.lastname: Rees
authors.affiliation: Research School of Biology, The Australian National University, Acton, Australian Capital Territory 2601, Australia.
authors.forename: Ben
authors.initials: B
authors.lastname: Corry
authors.affiliation: Department of Biochemistry and Molecular Biology, Institute for Biophysical Dynamics, University of Chicago, Chicago, Illinois 60637, USA.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Perozo
authors.affiliation: Division of Molecular Cardiology and Biophysics, Victor Chang Cardiac Research Institute, Darlinghurst, New South Wales 2010, Australia.|St Vincent's Clinical School, Faculty of Medicine, University of New South Wales, Darlinghurst, New South Wales 2010, Australia.
authors.forename: Boris
authors.identifier: 0000-0001-8422-7082
authors.initials: B
authors.lastname: Martinac
mesh_terms: D002462:Cell Membrane / Q000378:metabolism; D019295:Computational Biology; D004578:Electron Spin Resonance Spectroscopy; D004926:Escherichia coli / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000378:metabolism*; D017353:Gene Deletion; D015640:Ion Channel Gating; D007473:Ion Channels / Q000378:metabolism*; D008051:Lipid Bilayers / Q000737:chemistry; D008081:Liposomes / Q000737:chemistry; D040542:Mechanotransduction, Cellular; D008968:Molecular Conformation; D056004:Molecular Dynamics Simulation; D016297:Mutagenesis, Site-Directed; D018408:Patch-Clamp Techniques; D000072417:Protein Domains; D013816:Thermodynamics
chemical_list: D029968:Escherichia coli Proteins; D007473:Ion Channels; D008051:Lipid Bilayers; D008081:Liposomes; C086596:MscL protein, E coli