title: Selectivity mechanism of the mechanosensitive channel MscS revealed by probing channel subconducting states.
abstract: The mechanosensitive channel of small conductance (MscS) has been characterized at both functional and structural levels and has an integral role in the protection of bacterial cells against hypoosmotic shock. Here we investigate the role that the cytoplasmic domain has in MscS channel function by recording wild-type and mutant MscS single-channel activity in liposome patches. We report that MscS preferentially resides in subconducting states at hyperpolarising potentials when Ca(2+) and Ba(2+) ions are the major permeant cations. In addition, our results indicate that charged residues proximal to the seven vestibular portals and their electrostatic interactions with permeating cations determine selectivity and regulate the conductance of MscS and potentially other channels belonging to the MscS subfamily. Furthermore, our findings suggest a role for mechanosensitive channels in bacterial calcium regulation, indicative of functions other than protection against osmolarity changes that these channels possibly fulfil in bacteria.
authors.affiliation: School of Pharmacy and Pharmaceutical Sciences, Cardiff University, King Edward VII Avenue, Cardiff CF10 3NB, UK.
authors.forename: C D
authors.initials: CD
authors.lastname: Cox
authors.forename: T
authors.initials: T
authors.lastname: Nomura
authors.forename: C S
authors.initials: CS
authors.lastname: Ziegler
authors.forename: A K
authors.initials: AK
authors.lastname: Campbell
authors.forename: K T
authors.initials: KT
authors.lastname: Wann
authors.forename: B
authors.initials: B
authors.lastname: Martinac
mesh_terms: D001464:Barium / Q000737:chemistry / Q000378:metabolism; D002118:Calcium / Q000737:chemistry / Q000378:metabolism*; D002413:Cations, Divalent; D030562:Databases, Protein; D004926:Escherichia coli / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D029968:Escherichia coli Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D015640:Ion Channel Gating; D007473:Ion Channels / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D017136:Ion Transport; D008081:Liposomes / Q000737:chemistry; D040542:Mechanotransduction, Cellular / Q000502:physiology*; D008564:Membrane Potentials / Q000502:physiology*; D008958:Models, Molecular; D009154:Mutation; D017434:Protein Structure, Tertiary; D055672:Static Electricity; D046968:Thermoanaerobacter / Q000737:chemistry / Q000378:metabolism
chemical_list: D002413:Cations, Divalent; D029968:Escherichia coli Proteins; D007473:Ion Channels; D008081:Liposomes; C469542:MscS protein, E coli; D001464:Barium; D002118:Calcium