7F92

Structure of connexin43/Cx43/GJA1 gap junction intercellular channel in LMNG/CHS detergents at pH ~8.0

7F92 の概要

• エントリーDOI: 10.2210/pdb7f92/pdb
• EMDBエントリー: 31495
• 分子名称: Gap junction alpha-1 protein, TETRADECANE (3 entities in total)
• 機能のキーワード: cx43, connexin, gap junction channel, gating mechanism, membrane protein
• 由来する生物種: Homo sapiens (Human)
• タンパク質・核酸の鎖数: 12
• 化学式量合計: 542923.25

構造登録者

Lee, H.J.,Cha, H.J.,Jeong, H.,Lee, S.N.,Lee, C.W.,Woo, J.S. (登録日: 2021-07-03, 公開日: 2022-07-06, 最終更新日: 2024-10-23)

主引用文献

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

実験手法

ELECTRON MICROSCOPY (3.1 Å)