title: Hexadecameric structure of an invertebrate gap junction channel.
abstract: Innexins are invertebrate-specific gap junction proteins with four transmembrane helices. These proteins oligomerize to constitute intercellular channels that allow for the passage of small signaling molecules associated with neural and muscular electrical activity. In contrast to the large number of structural and functional studies of connexin gap junction channels, few structural studies of recombinant innexin channels are reported. Here we show the three-dimensional structure of two-dimensionally crystallized Caenorhabditis elegans innexin-6 (INX-6) gap junction channels. The N-terminal deleted INX-6 proteins are crystallized in lipid bilayers. The three-dimensional reconstruction determined by cryo-electron crystallography reveals that a single INX-6 gap junction channel comprises 16 subunits, a hexadecamer, in contrast to chordate connexin channels, which comprise 12 subunits. The channel pore diameters at the cytoplasmic entrance and extracellular gap region are larger than those of connexin26. Two bulb densities are observed in each hemichannel, one in the pore and the other at the cytoplasmic side of the hemichannel in the channel pore pathway. These findings imply a structural diversity of gap junction channels among multicellular organisms.
authors.affiliation: Cellular and Structural Physiology Institute (CeSPI), Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan; Department of Basic Medicinal Sciences, Graduate School of Pharmaceutical Sciences, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan. Electronic address: atsu@cespi.nagoya-u.ac.jp.
authors.forename: Atsunori
authors.initials: A
authors.lastname: Oshima
authors.affiliation: Department of Biophysics, Graduate School of Science, Kyoto University, Oiwake, Kitashirakawa, Sakyo-ku, Kyoto 606-8502, Japan.
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Matsuzawa
authors.affiliation: National Institute for Physiological Sciences, Okazaki, Aichi 444-8585, Japan.
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Murata
authors.affiliation: Cellular and Structural Physiology Institute (CeSPI), Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan.
authors.forename: Kazutoshi
authors.initials: K
authors.lastname: Tani
authors.affiliation: Cellular and Structural Physiology Institute (CeSPI), Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan; Department of Basic Medicinal Sciences, Graduate School of Pharmaceutical Sciences, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Fujiyoshi
mesh_terms: D000818:Animals; D017173:Caenorhabditis elegans / Q000737:chemistry / Q000648:ultrastructure; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry* / Q000378:metabolism*; D017630:Connexins / Q000737:chemistry* / Q000378:metabolism*; D020285:Cryoelectron Microscopy; D018360:Crystallography, X-Ray; D017629:Gap Junctions / Q000737:chemistry / Q000648:ultrastructure; D021621:Imaging, Three-Dimensional; D011487:Protein Conformation; D055503:Protein Multimerization
chemical_list: D029742:Caenorhabditis elegans Proteins; D017630:Connexins
keywords: cryo-electron crystallography; gap junction channel; innexin; three-dimensional reconstruction; two-dimensional crystal