title: Atomic structure of the innexin-6 gap junction channel determined by cryo-EM.
abstract: Innexins, a large protein family comprising invertebrate gap junction channels, play an essential role in nervous system development and electrical synapse formation. Here we report the cryo-electron microscopy structures of Caenorhabditis elegans innexin-6 (INX-6) gap junction channels at atomic resolution. We find that the arrangements of the transmembrane helices and extracellular loops of the INX-6 monomeric structure are highly similar to those of connexin-26 (Cx26), despite the lack of significant sequence similarity. The INX-6 gap junction channel comprises hexadecameric subunits but reveals the N-terminal pore funnel, consistent with Cx26. The helix-rich cytoplasmic loop and C-terminus are intercalated one-by-one through an octameric hemichannel, forming a dome-like entrance that interacts with N-terminal loops in the pore. These observations suggest that the INX-6 cytoplasmic domains are cooperatively associated with the N-terminal funnel conformation, and an essential linkage of the N-terminal with channel activity is presumably preserved across gap junction families.
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: Atsunori
authors.initials: A
authors.lastname: Oshima
authors.affiliation: Cellular and Structural Physiology Institute (CeSPI), Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8601, Japan.
authors.forename: Kazutoshi
authors.identifier: 0000-0003-4835-154X
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 / Q000378:metabolism*; D029742:Caenorhabditis elegans Proteins / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure*; D017630:Connexins / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure*; D020285:Cryoelectron Microscopy; D017629:Gap Junctions / Q000378:metabolism* / Q000648:ultrastructure*; D008958:Models, Molecular; D000072417:Protein Domains; D040681:Structural Homology, Protein
chemical_list: D029742:Caenorhabditis elegans Proteins; D017630:Connexins