Scientific article

Structure of the connexin-43 gap junction channel in a putative closed state

Published ineLife, vol. 12, RP87616
First online date2023-05-23

Gap junction channels (GJCs) mediate intercellular communication by connecting two neighboring 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 1-3 , 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 in nanodiscs reveal a similar gate arrangement. The features of the Cx43 GJC and hemichannel 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.

NoteDéposé dans: bioRxiv - 10.1101/2022.03.26.485947
Citation (ISO format)
QI, Chao et al. Structure of the connexin-43 gap junction channel in a putative closed state. In: eLife, 2023, vol. 12, p. RP87616. doi: 10.7554/eLife.87616.1
Main files (1)
Article (Submitted version)
ISSN of the journal2050-084X

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Creation03/28/2023 8:36:42 AM
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