{Reference Type}: Journal Article
{Title}: Structure of the connexin-43 gap junction channel in a putative closed state.
{Author}: Qi C;Acosta Gutierrez S;Lavriha P;Othman A;Lopez-Pigozzi D;Bayraktar E;Schuster D;Picotti P;Zamboni N;Bortolozzi M;Gervasio FL;Korkhov VM;
{Journal}: Elife
{Volume}: 12
{Issue}: 0
{Year}: 2023 08 3
{Factor}: 8.713
{DOI}: 10.7554/eLife.87616
{Abstract}: 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.