title: State-stabilizing Interactions in Bacterial Mechanosensitive Channel Gating and Adaptation.
abstract: We outline several principles that we believe define the gating of two bacterial mechanosensitive channels, MscL and MscS. Serving as turgor regulators in bacteria and other walled cells, these molecules are tangible models for studying conformational transitions in membrane proteins driven directly by membrane tension. MscL, a compact pentamer, reversibly opens a gigantic 30-A pore at near-lytic tensions. MscS, a heptameric complex, exhibits transient activation of a smaller pore at moderate tensions, thereby entering a tension-insensitive inactivated state. By comparing the structures and predicted transitions in these channels, we concluded that opening is commonly achieved through tilting and outward motion of the pore-lining helices, which is kinetically limited by hydration of the pore. The intricate adaptive behavior in MscS appears to depend on specific interhelical associations and the flexibility of the pore-lining helices. We discuss physical factors that may direct the transitions and stabilize main functional states in these channels.
authors.affiliation: Department of Biology, University of Maryland, College Park, Maryland 20742, USA.
authors.forename: Andriy
authors.initials: A
authors.lastname: Anishkin
authors.forename: Sergei
authors.initials: S
authors.lastname: Sukharev
mesh_terms: D000222:Adaptation, Physiological / Q000502:physiology*; D001426:Bacterial Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D029968:Escherichia coli Proteins / Q000737:chemistry / Q000235:genetics / Q000502:physiology; D015640:Ion Channel Gating / Q000502:physiology*; D007473:Ion Channels / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D040542:Mechanotransduction, Cellular / Q000502:physiology; D008958:Models, Molecular; D009154:Mutation; D011487:Protein Conformation
chemical_list: D001426:Bacterial Proteins; D029968:Escherichia coli Proteins; D007473:Ion Channels; C086596:MscL protein, E coli; C469542:MscS protein, E coli