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TitleStructure of the connexin-43 gap junction channel in a putative closed state.
Journal, issue, pagesElife, Vol. 12, Year 2023
Publish dateAug 3, 2023
AuthorsChao 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 AbstractGap 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.
External linksElife / PubMed:37535063 / PubMed Central
MethodsEM (single particle)
Resolution2.26 - 3.98 Å
Structure data

EMDB-14452, PDB-7z1t:
Connexin43 gap junction channel structure in digitonin
Method: EM (single particle) / Resolution: 2.26 Å

EMDB-14455, PDB-7z22:
Connexin43 gap junction channel structure in nanodisc
Method: EM (single particle) / Resolution: 2.95 Å

EMDB-14456: Connexin43 gap junction channel structure in digitonin
PDB-7z23: Connexin43 hemi channel in nanodisc
Method: EM (single particle) / Resolution: 3.98 Å

Source
  • homo sapiens (human)
KeywordsMEMBRANE PROTEIN / gap junction channel / connexin / cell communication

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