title: X-ray crystal structure of voltage-gated proton channel.
abstract: The voltage-gated proton channel Hv1 (or VSOP) has a voltage-sensor domain (VSD) with dual roles of voltage sensing and proton permeation. Its gating is sensitive to pH and Zn(2+). Here we present a crystal structure of mouse Hv1 in the resting state at 3.45-Å resolution. The structure showed a 'closed umbrella' shape with a long helix consisting of the cytoplasmic coiled coil and the voltage-sensing helix, S4, and featured a wide inner-accessible vestibule. Two out of three arginines in S4 were located below the phenylalanine constituting the gating charge-transfer center. The extracellular region of each protomer coordinated a Zn(2+), thus suggesting that Zn(2+) stabilizes the resting state of Hv1 by competing for acidic residues that otherwise form salt bridges with voltage-sensing positive charges on S4. These findings provide a platform for understanding the general principles of voltage sensing and proton permeation.
authors.affiliation: 1] Institute for Protein Research, Osaka University, Suita, Japan. [2] Graduate School of Medicine, Osaka University, Suita, Japan. [3] Institute for Academic Initiatives, Osaka University, Suita, Japan.
authors.forename: Kohei
authors.initials: K
authors.lastname: Takeshita
authors.affiliation: 1] Graduate School of Medicine, Osaka University, Suita, Japan. [2] Institute for Academic Initiatives, Osaka University, Suita, Japan.
authors.forename: Souhei
authors.initials: S
authors.lastname: Sakata
authors.affiliation: Institute for Protein Research, Osaka University, Suita, Japan.
authors.forename: Eiki
authors.initials: E
authors.lastname: Yamashita
authors.affiliation: Graduate School of Medicine, Osaka University, Suita, Japan.
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Fujiwara
authors.affiliation: Graduate School of Medicine, Osaka University, Suita, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Kawanabe
authors.affiliation: 1] Graduate School of Medicine, Osaka University, Suita, Japan. [2] Present address: Graduate School of Engineering, Kyoto University, Kyoto, Japan.
authors.forename: Tatsuki
authors.initials: T
authors.lastname: Kurokawa
authors.affiliation: Graduate School of Medicine, Osaka University, Suita, Japan.
authors.forename: Yoshifumi
authors.initials: Y
authors.lastname: Okochi
authors.affiliation: Institute for Protein Research, Osaka University, Suita, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Matsuda
authors.affiliation: Institute for Protein Research, Osaka University, Suita, Japan.
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Narita
authors.affiliation: 1] Graduate School of Medicine, Osaka University, Suita, Japan. [2] Institute for Academic Initiatives, Osaka University, Suita, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Okamura
authors.affiliation: 1] Institute for Protein Research, Osaka University, Suita, Japan. [2] Institute for Academic Initiatives, Osaka University, Suita, Japan.
authors.forename: Atsushi
authors.identifier: 0000000217007861
authors.initials: A
authors.lastname: Nakagawa
mesh_terms: D000818:Animals; D018360:Crystallography, X-Ray; D019281:Dimerization; D015640:Ion Channel Gating; D007473:Ion Channels / Q000737:chemistry*; D016350:Leucine Zippers; D051379:Mice; D008958:Models, Molecular; D017434:Protein Structure, Tertiary; D011522:Protons; D012441:Saccharomyces cerevisiae / Q000235:genetics; D013816:Thermodynamics; D014965:X-Rays; D015032:Zinc / Q000737:chemistry
chemical_list: C540876:Hv1 proton channel, mouse; D007473:Ion Channels; D011522:Protons; D015032:Zinc