title: Structural investigation of MscL gating using experimental data and coarse grained MD simulations.
abstract: The mechanosensitive channel of large conductance (MscL) has become a model system in which to understand mechanosensation, a process involved in osmoregulation and many other physiological functions. While a high resolution closed state structure is available, details of the open structure and the gating mechanism remain unknown. In this study we combine coarse grained simulations with restraints from EPR and FRET experiments to study the structural changes involved in gating with much greater level of conformational sampling than has previously been possible. We generated a set of plausible open pore structures that agree well with existing open pore structures and gating models. Most interestingly, we found that membrane thinning induces a kink in the upper part of TM1 that causes an outward motion of the periplasmic loop away from the pore centre. This previously unobserved structural change might present a new mechanism of tension sensing and might be related to a functional role in osmoregulation.
authors.affiliation: School of Biomedical, Biomolecular and Chemical Sciences, The University of Western Australia, Perth, Australia.
authors.forename: Evelyne
authors.initials: E
authors.lastname: Deplazes
authors.forename: Martti
authors.initials: M
authors.lastname: Louhivuori
authors.forename: Dylan
authors.initials: D
authors.lastname: Jayatilaka
authors.forename: Siewert J
authors.initials: SJ
authors.lastname: Marrink
authors.forename: Ben
authors.initials: B
authors.lastname: Corry
mesh_terms: D003198:Computer Simulation; D029968:Escherichia coli Proteins / Q000737:chemistry* / Q000648:ultrastructure*; D015640:Ion Channel Gating; D007473:Ion Channels / Q000737:chemistry* / Q000648:ultrastructure*; D040542:Mechanotransduction, Cellular; D008956:Models, Chemical; D056004:Molecular Dynamics Simulation; D016062:Porosity; D011487:Protein Conformation; D013314:Stress, Mechanical; D013329:Structure-Activity Relationship
chemical_list: D029968:Escherichia coli Proteins; D007473:Ion Channels; C086596:MscL protein, E coli