title: Gating of the designed trimeric/tetrameric voltage-gated H+ channel.
abstract: The voltage-gated H(+) channel functions as a dimer, a configuration that is different from standard tetrameric voltage-gated channels. Each channel protomer has its own permeation pathway. The C-terminal coiled-coil domain has been shown to be necessary for both dimerization and cooperative gating in the two channel protomers. Here we report the gating cooperativity in trimeric and tetrameric Hv channels engineered by altering the hydrophobic core sequence of the coiled-coil assembly domain. Trimeric and tetrameric channels exhibited more rapid and less sigmoidal kinetics of activation of H(+) permeation than dimeric channels, suggesting that some channel protomers in trimers and tetramers failed to produce gating cooperativity observed in wild-type dimers. Multimerization of trimer and tetramer channels were confirmed by the biochemical analysis of proteins, including crystallography. These findings indicate that the voltage-gated H(+) channel is optimally designed as a dimeric channel on a solid foundation of the sequence pattern of the coiled-coil core, with efficient cooperative gating that ensures sustained and steep voltage-dependent H(+) conductance in blood cells.
authors.affiliation: Laboratory of Integrative Physiology, Department of Physiology, Graduate School of Medicine, Osaka University, Suita, Osaka, Japan. fujiwara@phys2.med.osaka-u.ac.jp
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Fujiwara
authors.forename: Tatsuki
authors.initials: T
authors.lastname: Kurokawa
authors.forename: Kohei
authors.initials: K
authors.lastname: Takeshita
authors.forename: Atsushi
authors.initials: A
authors.lastname: Nakagawa
authors.forename: H Peter
authors.initials: HP
authors.lastname: Larsson
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Okamura
mesh_terms: D057809:HEK293 Cells; D006801:Humans; D015640:Ion Channel Gating; D007473:Ion Channels / Q000737:chemistry / Q000235:genetics / Q000502:physiology*; D009154:Mutation; D055503:Protein Multimerization; D017434:Protein Structure, Tertiary; D021122:Protein Subunits
chemical_list: C540876:Hv1 proton channel, mouse; D007473:Ion Channels; D021122:Protein Subunits