7XQH

Hemichannel-focused structure of C-terminal truncated connexin43/Cx43/GJA1 gap junction intercellular channel in POPE nanodiscs (GCN-TM1i conformation)

Summary for 7XQH

• Entry DOI: 10.2210/pdb7xqh/pdb
• EMDB information: 33396
• Descriptor: C-terminal deletion mutant of gap junction alpha-1 protein (Cx43-M257) (1 entity in total)
• Functional Keywords: cx43, connexin, gap junction channel, gating mechanism, membrane protein
• Biological source: Homo sapiens (human)
• Total number of polymer chains: 6
• Total formula weight: 176379.28

Authors

Lee, H.J.,Cha, H.J.,Jeong, H.,Lee, S.N.,Lee, C.W.,Woo, J.S. (deposition date: 2022-05-07, release date: 2023-01-25, Last modification date: 2024-10-30)

Primary citation

Lee, H.J.,Cha, H.J.,Jeong, H.,Lee, S.N.,Lee, C.W.,Kim, M.,Yoo, J.,Woo, J.S.
Conformational changes in the human Cx43/GJA1 gap junction channel visualized using cryo-EM.
Nat Commun, 14:931-931, 2023

PubMed Abstract: Connexin family proteins assemble into hexameric hemichannels in the cell membrane. The hemichannels dock together between two adjacent membranes to form gap junction intercellular channels (GJIChs). We report the cryo-electron microscopy structures of Cx43 GJICh, revealing the dynamic equilibrium state of various channel conformations in detergents and lipid nanodiscs. We identify three different N-terminal helix conformations of Cx43-gate-covering (GCN), pore-lining (PLN), and flexible intermediate (FIN)-that are randomly distributed in purified GJICh particles. The conformational equilibrium shifts to GCN by cholesteryl hemisuccinates and to PLN by C-terminal truncations and at varying pH. While GJIChs that mainly comprise GCN protomers are occluded by lipids, those containing conformationally heterogeneous protomers show markedly different pore sizes. We observe an α-to-π-helix transition in the first transmembrane helix, which creates a side opening to the membrane in the FIN and PLN conformations. This study provides basic structural information to understand the mechanisms of action and regulation of Cx43 GJICh.

PubMed: 36805660
DOI: 10.1038/s41467-023-36593-y

Experimental method

ELECTRON MICROSCOPY (3.8 Å)