title: Direct Interaction between the Voltage Sensors Produces Cooperative Sustained Deactivation in Voltage-gated H+ Channel Dimers.
abstract: The voltage-gated H(+) channel (Hv) is a voltage sensor domain-like protein consisting of four transmembrane segments (S1-S4). The native Hv structure is a homodimer, with the two channel subunits functioning cooperatively. Here we show that the two voltage sensor S4 helices within the dimer directly cooperate via a π-stacking interaction between Trp residues at the middle of each segment. Scanning mutagenesis showed that Trp situated around the original position provides the slow gating kinetics characteristic of the dimer's cooperativity. Analyses of the Trp mutation on the dimeric and monomeric channel backgrounds and analyses with tandem channel constructs suggested that the two Trp residues within the dimer are functionally coupled during Hv deactivation but are less so during activation. Molecular dynamics simulation also showed direct π-stacking of the two Trp residues. These results provide new insight into the cooperative function of voltage-gated channels, where adjacent voltage sensor helices make direct physical contact and work as a single unit according to the gating process.
authors.affiliation: From Division of Integrative Physiology, Graduate School of Medicine.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Okuda
authors.affiliation: the High Pressure Protein Research Center, Institute of Advanced Technology, Kinki University, Kinokawa 649-6493, Wakayama, Japan, and.
authors.forename: Yasushige
authors.initials: Y
authors.lastname: Yonezawa
authors.affiliation: the Institute for Protein Research, and; the Graduate School of Information Sciences, Hiroshima City University, Hiroshima 731-3194, Hiroshima, Japan.
authors.forename: Yu
authors.initials: Y
authors.lastname: Takano
authors.affiliation: From Division of Integrative Physiology, Graduate School of Medicine,; the Graduate School of Frontier Biosciences, Osaka University, Suita 565-0871, Osaka, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Okamura
authors.affiliation: From Division of Integrative Physiology, Graduate School of Medicine,. Electronic address: fujiwara@phys2.med.osaka-u.ac.jp.
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Fujiwara
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D015640:Ion Channel Gating; D007473:Ion Channels / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D056004:Molecular Dynamics Simulation; D008969:Molecular Sequence Data; D016296:Mutagenesis; D011487:Protein Conformation; D055503:Protein Multimerization; D017433:Protein Structure, Secondary; D016415:Sequence Alignment; D014561:Urochordata / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014981:Xenopus
chemical_list: D007473:Ion Channels
keywords: channel gating; ion channel; membrane biophysics; oocyte; proton transport; structure-function; voltage-gated channel