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-Structure paper
タイトル | Structure of the connexin-43 gap junction channel in a putative closed state. |
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ジャーナル・号・ページ | Elife, Vol. 12, Year 2023 |
掲載日 | 2023年8月3日 |
著者 | Chao Qi / Silvia Acosta Gutierrez / Pia Lavriha / Alaa Othman / Diego Lopez-Pigozzi / Erva Bayraktar / Dina Schuster / Paola Picotti / Nicola Zamboni / Mario Bortolozzi / Francesco Luigi Gervasio / Volodymyr M Korkhov / |
PubMed 要旨 | Gap junction channels (GJCs) mediate intercellular communication by connecting two neighbouring cells and enabling direct exchange of ions and small molecules. Cell coupling via connexin-43 (Cx43) ...Gap junction channels (GJCs) mediate intercellular communication by connecting two neighbouring cells and enabling direct exchange of ions and small molecules. Cell coupling via connexin-43 (Cx43) GJCs is important in a wide range of cellular processes in health and disease (Churko and Laird, 2013; Liang et al., 2020; Poelzing and Rosenbaum, 2004), yet the structural basis of Cx43 function and regulation has not been determined until now. Here, we describe the structure of a human Cx43 GJC solved by cryo-EM and single particle analysis at 2.26 Å resolution. The pore region of Cx43 GJC features several lipid-like densities per Cx43 monomer, located close to a putative lateral access site at the monomer boundary. We found a previously undescribed conformation on the cytosolic side of the pore, formed by the N-terminal domain and the transmembrane helix 2 of Cx43 and stabilized by a small molecule. Structures of the Cx43 GJC and hemichannels (HCs) in nanodiscs reveal a similar gate arrangement. The features of the Cx43 GJC and HC cryo-EM maps and the channel properties revealed by molecular dynamics simulations suggest that the captured states of Cx43 are consistent with a closed state. |
リンク | Elife / PubMed:37535063 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 2.26 - 3.98 Å |
構造データ | EMDB-14452, PDB-7z1t: EMDB-14455, PDB-7z22: EMDB-14456: Connexin43 gap junction channel structure in digitonin |
由来 |
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キーワード | MEMBRANE PROTEIN / gap junction channel / connexin / cell communication |