ジャーナル: Nat Commun / 年: 2023 タイトル: Conformational changes in the human Cx43/GJA1 gap junction channel visualized using cryo-EM. 著者: Hyuk-Joon Lee / Hyung Jin Cha / Hyeongseop Jeong / Seu-Na Lee / Chang-Won Lee / Minsoo Kim / Jejoong Yoo / Jae-Sung Woo / 要旨: 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.
全体 : Dodecameric complex of human Cx43/GJA1 in detergents (LMNG/CHS) a...
全体
名称: Dodecameric complex of human Cx43/GJA1 in detergents (LMNG/CHS) at pH ~6.9
要素
複合体: Dodecameric complex of human Cx43/GJA1 in detergents (LMNG/CHS) at pH ~6.9
タンパク質・ペプチド: Gap junction alpha-1 protein (Cx43)
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超分子 #1: Dodecameric complex of human Cx43/GJA1 in detergents (LMNG/CHS) a...
超分子
名称: Dodecameric complex of human Cx43/GJA1 in detergents (LMNG/CHS) at pH ~6.9 タイプ: complex / ID: 1 / キメラ: Yes / 親要素: 0 / 含まれる分子: all 詳細: Human Cx43 gap junction channel composed of two different protomers in pore-lining and gate-covering NTH conformations
由来(天然)
生物種: Homo sapiens (ヒト)
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分子 #1: Gap junction alpha-1 protein (Cx43)
分子
名称: Gap junction alpha-1 protein (Cx43) / タイプ: protein_or_peptide / ID: 1 / 光学異性体: LEVO