title: Simulation of MscL gating in a bilayer under stress.
abstract: The initial stages of the gating of the mechanoselective channel of large conductance from Mycobacterium tuberculosis have been studied in atomic detail using molecular dynamics simulation techniques. A truncated form of the protein complex embedded in a palmitoyloleoylphosphatidylcholine lipid bilayer and surrounded by explicit water was simulated under different pressure conditions to mimic the effects of tension and compression within the membrane on the protein. As a direct result of lateral tension being applied to the membrane, an increase in the tilt of a subset of the transmembrane helices was observed. This in turn led to the enlargement of the pore and the disruption of the hydrophobic gate consisting of residues Ile-14 and Val-21. The simulations suggest that opening occurs in a sequential staged process. Such a mechanism could explain the partial opening or staged conductance observed in patch-clamp experiments using related large conductance mechanosensitive channel complexes.
authors.affiliation: Istituto di Chimica del Riconoscimento Molecolare, CNR, 20131 Milan, Italy. colombo@icrm.cnr.it
authors.forename: Giorgio
authors.initials: G
authors.lastname: Colombo
authors.forename: Siewert Jan
authors.initials: SJ
authors.lastname: Marrink
authors.forename: Alan E
authors.initials: AE
authors.lastname: Mark
mesh_terms: D032701:Biomimetics / Q000379:methods*; D002463:Cell Membrane Permeability; D019245:Compressive Strength; D003198:Computer Simulation; D057927:Hydrophobic and Hydrophilic Interactions; D015640:Ion Channel Gating; D008051:Lipid Bilayers / Q000737:chemistry*; D040542:Mechanotransduction, Cellular; D008560:Membrane Fluidity; D008958:Models, Molecular; D009038:Motion; D010713:Phosphatidylcholines / Q000737:chemistry*; D016062:Porosity; D011312:Pressure; D011487:Protein Conformation; D017433:Protein Structure, Secondary; D021122:Protein Subunits; D013314:Stress, Mechanical; D013718:Tensile Strength; D014867:Water / Q000737:chemistry
chemical_list: D008051:Lipid Bilayers; D010713:Phosphatidylcholines; D021122:Protein Subunits; D014867:Water; C028694:1-palmitoyl-2-oleoylphosphatidylcholine