7Z22

Connexin43 gap junction channel structure in nanodisc

7Z22 の概要

• エントリーDOI: 10.2210/pdb7z22/pdb
• 関連するPDBエントリー: 7Z1T
• EMDBエントリー: 14455
• 分子名称: Gap junction alpha-1 protein (1 entity in total)
• 機能のキーワード: gap junction channel, connexin, cell communication, 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: 516736.03

構造登録者

Qi, C.,Korkhov, M.V. (登録日: 2022-02-25, 公開日: 2023-03-08, 最終更新日: 2024-10-16)

主引用文献

Qi, C.,Acosta Gutierrez, S.,Lavriha, P.,Othman, A.,Lopez-Pigozzi, D.,Bayraktar, E.,Schuster, D.,Picotti, P.,Zamboni, N.,Bortolozzi, M.,Gervasio, F.L.,Korkhov, V.M.
Structure of the connexin-43 gap junction channel in a putative closed state.
Elife, 12:-, 2023

PubMed Abstract: Gap junction channels (GJCs) mediate intercellular communication by connecting two neighbouring 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 (Churko and Laird, 2013; Liang et al., 2020; Poelzing and Rosenbaum, 2004), yet the structural basis of Cx43 function and regulation has not been determined until now. Here, we describe the structure of a 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 conformation 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 (HCs) in nanodiscs reveal a similar gate arrangement. The features of the Cx43 GJC and HC cryo-EM maps and the channel properties revealed by molecular dynamics simulations suggest that the captured states of Cx43 are consistent with a closed state.

PubMed: 37535063
DOI: 10.7554/eLife.87616

実験手法

ELECTRON MICROSCOPY (2.95 Å)