title: Gating mechanisms of voltage-gated proton channels.
abstract: Hv1 is a voltage-gated proton-selective channel that plays critical parts in host defense, sperm motility, and cancer progression. Hv1 contains a conserved voltage-sensor domain (VSD) that is shared by a large family of voltage-gated ion channels, but it lacks a pore domain. Voltage sensitivity and proton conductivity are conferred by a unitary VSD that consists of four transmembrane helices. The architecture of Hv1 differs from that of cation channels that form a pore in the center among multiple subunits (as in most cation channels) or homologous repeats (as in voltage-gated sodium and calcium channels). Hv1 forms a dimer in which a cytoplasmic coiled coil underpins the two protomers and forms a single, long helix that is contiguous with S4, the transmembrane voltage-sensing segment. The closed-state structure of Hv1 was recently solved using X-ray crystallography. In this article, we discuss the gating mechanism of Hv1 and focus on cooperativity within dimers and their sensitivity to metal ions.
authors.affiliation: Department of Integrative Physiology, Graduate School of Medicine, Osaka University, Osaka 565-0871, Japan; email: yokamura@phys2.med.osaka-u.ac.jp , fujiwara@phys2.med.osaka-u.ac.jp , sakata@phys2.med.osaka-u.ac.jp.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Okamura
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Fujiwara
authors.forename: Souhei
authors.initials: S
authors.lastname: Sakata
mesh_terms: D000818:Animals; D018360:Crystallography, X-Ray; D006801:Humans; D007473:Ion Channels / Q000737:chemistry* / Q000378:metabolism*; D008958:Models, Molecular
chemical_list: C510235:HVCN1 protein, human; D007473:Ion Channels
keywords: arginine residue; membrane potential; reactive oxygen species; salt bridge; zinc binding