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Title | Conformational changes in the human Cx43/GJA1 gap junction channel visualized using cryo-EM. |
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Journal, issue, pages | Nat Commun, Vol. 14, Issue 1, Page 931, Year 2023 |
Publish date | Feb 18, 2023 |
Authors | Hyuk-Joon Lee / Hyung Jin Cha / Hyeongseop Jeong / Seu-Na Lee / Chang-Won Lee / Minsoo Kim / Jejoong Yoo / Jae-Sung Woo / |
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). ...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. |
External links | Nat Commun / PubMed:36805660 / PubMed Central |
Methods | EM (single particle) |
Resolution | 2.3 - 4.0 Å |
Structure data | EMDB-31495, PDB-7f92: EMDB-31496, PDB-7f93: EMDB-31497, PDB-7f94: EMDB-33391, PDB-7xq9: EMDB-33392, PDB-7xqb: EMDB-33393, PDB-7xqd: EMDB-33394, PDB-7xqf: EMDB-33395, PDB-7xqg: EMDB-33396, PDB-7xqh: EMDB-33397, PDB-7xqi: EMDB-33398, PDB-7xqj: EMDB-33399: Consensus map of connexin43/Cx43/GJA1 gap junction intercellular channel in LMNG/CHS detergents at pH ~6.9 |
Chemicals | ChemComp-C14: ChemComp-HOH: ChemComp-Y01: ChemComp-PTY: |
Source |
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Keywords | MEMBRANE PROTEIN / Cx43 / Connexin / Gap junction channel / Gating mechanism |