title: The C-terminal helical bundle of the tetrameric prokaryotic sodium channel accelerates the inactivation rate.
abstract: Most tetrameric channels have cytosolic domains to regulate their functions, including channel inactivation. Here we show that the cytosolic C-terminal region of NavSulP, a prokaryotic voltage-gated sodium channel cloned from Sulfitobacter pontiacus, accelerates channel inactivation. The crystal structure of the C-terminal region of NavSulP grafted into the C-terminus of a NaK channel revealed that the NavSulP C-terminal region forms a four-helix bundle. Point mutations of the residues involved in the intersubunit interactions of the four-helix bundle destabilized the tetramer of the channel and reduced the inactivation rate. The four-helix bundle was directly connected to the inner helix of the pore domain, and a mutation increasing the rigidity of the inner helix also reduced the inactivation rate. These findings suggest that the NavSulP four-helix bundle has important roles not only in stabilizing the tetramer, but also in accelerating the inactivation rate, through promotion of the conformational change of the inner helix.
authors.affiliation: Department of Biophysics, Graduate School of Science, Kyoto University, Oiwake, Kitashirakawa, Sakyo-ku, Kyoto 606-8502, Japan.
authors.forename: Katsumasa
authors.initials: K
authors.lastname: Irie
authors.forename: Takushi
authors.initials: T
authors.lastname: Shimomura
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Fujiyoshi
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D001426:Bacterial Proteins / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D018360:Crystallography, X-Ray; D007700:Kinetics; D008958:Models, Molecular; D008969:Molecular Sequence Data; D010802:Phylogeny; D017354:Point Mutation; D055503:Protein Multimerization; D017434:Protein Structure, Tertiary; D041902:Rhodobacteraceae / Q000737:chemistry / Q000145:classification / Q000235:genetics / Q000378:metabolism*; D015222:Sodium Channels / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
chemical_list: D001426:Bacterial Proteins; D015222:Sodium Channels