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Volodymyr KORKHOV - Colloquia in Cellular Signaling


13. Mai 2022
11:00 - 12:00

Medical University Vienna, Center for Physiology and Pharmacology,
Institute of Pharmacology, Waehringerstrasse 13a, 1090 Vienna

Großer Hörsaal Physiologie (big lecture hall Physiology)

Volodymyr KORKHOV
Paul Scherrer Institute
Forschungsstrasse 111
5232 Villigen PSI
Website Korkhov research group


”Structure of the connexin-43 gap junction channel reveals a closed sieve-like molecular gate”

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, yet the structural basis of Cx43 function and regulation has not been determined until recently. I will present our structure of the 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 closed sieve-like gate 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 confirm the sieve-like 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 closed. 

Host: Harald SITTE

Contact for questions: Helmut KUBISTA