title: Functional interactions at the interface between voltage-sensing and pore domains in the Shaker K(v) channel.
abstract: Voltage-activated potassium (K(v)) channels contain a central pore domain that is partially surrounded by four voltage-sensing domains. Recent X-ray structures suggest that the two domains lack extensive protein-protein contacts within presumed transmembrane regions, but whether this is the case for functional channels embedded in lipid membranes remains to be tested. We investigated domain interactions in the Shaker K(v) channel by systematically mutating the pore domain and assessing tolerance by examining channel maturation, S4 gating charge movement, and channel opening. When mapped onto the X-ray structure of the K(v)1.2 channel the large number of permissive mutations support the notion of relatively independent domains, consistent with crystallographic studies. Inspection of the maps also identifies portions of the interface where residues are sensitive to mutation, an external cluster where mutations hinder voltage sensor activation, and an internal cluster where domain interactions between S4 and S5 helices from adjacent subunits appear crucial for the concerted opening transition.
authors.affiliation: Molecular Physiology and Biophysics Section, Porter Neuroscience Research Center, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892, USA.
authors.forename: Gilberto J
authors.initials: GJ
authors.lastname: Soler-Llavina
authors.forename: Tsg-Hui
authors.initials: TH
authors.lastname: Chang
authors.forename: Kenton J
authors.initials: KJ
authors.lastname: Swartz
mesh_terms: D000818:Animals; D002462:Cell Membrane / Q000235:genetics / Q000378:metabolism* / Q000648:ultrastructure; D018360:Crystallography, X-Ray; D005260:Female; D015640:Ion Channel Gating / Q000502:physiology*; D051663:Kv1.2 Potassium Channel / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D008564:Membrane Potentials / Q000235:genetics; D008958:Models, Molecular; D009154:Mutation / Q000235:genetics; D009865:Oocytes; D017433:Protein Structure, Secondary / Q000235:genetics; D017434:Protein Structure, Tertiary / Q000235:genetics; D051637:Shaker Superfamily of Potassium Channels / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014982:Xenopus laevis
chemical_list: D051663:Kv1.2 Potassium Channel; D051637:Shaker Superfamily of Potassium Channels