title: Solution structure of the sodium channel inactivation gate.
abstract: The sodium channel initiates action potentials by opening in response to membrane depolarization. Fast channel inactivation, which is required for proper physiological function, is mediated by a cytoplasmic loop proposed to occlude the ion pore via a hinged lid mechanism with the triad IFM serving as a hydrophobic "latch". The NMR solution structure of the isolated inactivation gate reveals a stably folded core comprised of an alpha-helix capped by an N-terminal turn, supporting a model in which the tightly folded core containing the latch motif pivots on a more flexible hinge region to occlude the pore during inactivation. The structure, in combination with substituted cysteine mutagenesis experiments, indicates that the IFM triad and adjacent Thr are essential components of the latch and suggests differing roles for the residues of the IFMT motif in fast inactivation.
authors.affiliation: Department of Biochemistry, University of Washington, Seattle 98195, USA.
authors.forename: C A
authors.initials: CA
authors.lastname: Rohl
authors.forename: F A
authors.initials: FA
authors.lastname: Boeckman
authors.forename: C
authors.initials: C
authors.lastname: Baker
authors.forename: T
authors.initials: T
authors.lastname: Scheuer
authors.forename: W A
authors.initials: WA
authors.lastname: Catterall
authors.forename: R E
authors.initials: RE
authors.lastname: Klevit
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001923:Brain Chemistry; D018360:Crystallography, X-Ray; D015640:Ion Channel Gating; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009479:Neuropeptides / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000502:physiology; D019906:Nuclear Magnetic Resonance, Biomolecular; D051381:Rats; D026941:Sodium Channel Blockers; D015222:Sodium Channels / Q000737:chemistry* / Q000502:physiology; D012996:Solutions
chemical_list: D009479:Neuropeptides; D026941:Sodium Channel Blockers; D015222:Sodium Channels; D012996:Solutions