Qi, Chao;
Acosta Gutierrez, Silvia;
Lavriha, Pia;
Othman, Alaa;
Lopez-Pigozzi, Diego;
Bayraktar, Erva;
Schuster, Dina;
... Korkhov, Volodymyr M; + view all
(2023)
Structure of the connexin-43 gap junction channel in a putative closed state.
eLife
, 12
, Article RP87616. 10.7554/eLife.87616.
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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.
| Type: | Article |
|---|---|
| Title: | Structure of the connexin-43 gap junction channel in a putative closed state |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.7554/eLife.87616 |
| Publisher version: | https://doi.org/10.7554/eLife.87616 |
| Language: | English |
| Additional information: | Copyright Qi, Acosta Gutierrez et al. This article is distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use and redistribution provided that the original author and source are credited. |
| Keywords: | Biochemistry, chemical biology, connexin-43, cryo-EM, gap junction channel, hemichannel, human, membrane protein, molecular biophysics, structural biology, structure, Humans, Cell Communication, Connexin 43, Gap Junctions, Ion Channels |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > UCL BEAMS UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences UCL > Provost and Vice Provost Offices > UCL BEAMS > Faculty of Maths and Physical Sciences > Dept of Chemistry |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/10174765 |
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