title: Long α helices projecting from the membrane as the dimer interface in the voltage-gated H(+) channel.
abstract: The voltage-gated H(+) channel (Hv) is a H(+)-permeable voltage-sensor domain (VSD) protein that consists of four transmembrane segments (S1-S4). Hv assembles as a dimeric channel and two transmembrane channel domains function cooperatively, which is mediated by the coiled-coil assembly domain in the cytoplasmic C terminus. However, the structural basis of the interdomain interactions remains unknown. Here, we provide a picture of the dimer configuration based on the analyses of interactions among two VSDs and a coiled-coil domain. Systematic mutations of the linker region between S4 of VSD and the coiled-coil showed that the channel gating was altered in the helical periodicity with the linker length, suggesting that two domains are linked by helices. Cross-linking analyses revealed that the two S4 helices were situated closely in the dimeric channel. The interaction interface between the two S4 and the assembly interface of the coiled-coil domain were aligned in the same direction based on the phase angle calculation along α helices. Collectively, we propose that continuous helices stretching from the transmembrane to the cytoplasmic region in the dimeric interface regulate the channel activation in the Hv dimer.
authors.affiliation: Integrative Physiology, Graduate School of Medicine, and 2 Graduate School of Frontier Biosciences, Osaka University, Osaka 565-0871, Japan.
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Fujiwara
authors.forename: Tatsuki
authors.initials: T
authors.lastname: Kurokawa
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Okamura
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D002462:Cell Membrane / Q000737:chemistry / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D015640:Ion Channel Gating; D007473:Ion Channels / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008969:Molecular Sequence Data; D009154:Mutation; D055503:Protein Multimerization; D017434:Protein Structure, Tertiary
chemical_list: C540876:Hv1 proton channel, mouse; D007473:Ion Channels