title: A gating hinge in Na+ channels; a molecular switch for electrical signaling.
abstract: Voltage-gated sodium channels are members of a large family with similar pore structures. The mechanism of opening and closing is unknown, but structural studies suggest gating via bending of the inner pore helix at a glycine hinge. Here we provide functional evidence for this gating model for the bacterial sodium channel NaChBac. Mutation of glycine 219 to proline, which would strongly favor bending of the alpha helix, greatly enhances activation by shifting its voltage dependence -51 mV and slowing deactivation by 2000-fold. The mutation also slows voltage-dependent inactivation by 1200-fold. The effects are specific because substitutions of proline at neighboring positions and substitutions of other amino acids at position 219 have much smaller functional effects. Our results fit a model in which concerted bending at glycine 219 in the S6 segments of NaChBac serves as a gating hinge. This gating motion may be conserved in most members of this large ion channel protein family.
authors.affiliation: Department of Pharmacology, Box 357280, University of Washington, Seattle, WA 98105, USA.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhao
authors.forename: Vladimir
authors.initials: V
authors.lastname: Yarov-Yarovoy
authors.forename: Todd
authors.initials: T
authors.lastname: Scheuer
authors.forename: William A
authors.initials: WA
authors.lastname: Catterall
mesh_terms: D001407:Bacillus; D001426:Bacterial Proteins / Q000235:genetics* / Q000378:metabolism*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D019143:Evolution, Molecular; D005998:Glycine / Q000378:metabolism; D006801:Humans; D015640:Ion Channel Gating / Q000235:genetics / Q000502:physiology*; D008564:Membrane Potentials / Q000235:genetics; D008958:Models, Molecular; D009154:Mutation / Q000235:genetics; D018408:Patch-Clamp Techniques; D011392:Proline / Q000378:metabolism; D017433:Protein Structure, Secondary / Q000235:genetics; D015222:Sodium Channels / Q000235:genetics* / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; C443666:NaChBac protein, bacteria; D015222:Sodium Channels; D011392:Proline; D005998:Glycine