6UVR

Human Connexin-26 (Neutral pH open conformation)

6UVR の概要

• エントリーDOI: 10.2210/pdb6uvr/pdb
• 関連するPDBエントリー: 6UVS 6UVT
• EMDBエントリー: 20914 20915 20916
• 分子名称: Gap junction beta-2 protein (1 entity in total)
• 機能のキーワード: gap junction channel, 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: 314579.34

構造登録者

Khan, A.K.,Jagielnicki, M.,Purdy, M.D.,Yeager, M. (登録日: 2019-11-04, 公開日: 2020-04-29, 最終更新日: 2024-11-06)

主引用文献

Khan, A.K.,Jagielnicki, M.,McIntire, W.E.,Purdy, M.D.,Dharmarajan, V.,Griffin, P.R.,Yeager, M.
A Steric "Ball-and-Chain" Mechanism for pH-Mediated Regulation of Gap Junction Channels.
Cell Rep, 31:107482-107482, 2020

PubMed Abstract: Gap junction channels (GJCs) mediate intercellular communication and are gated by numerous conditions such as pH. The electron cryomicroscopy (cryo-EM) structure of Cx26 GJC at physiological pH recapitulates previous GJC structures in lipid bilayers. At pH 6.4, we identify two conformational states, one resembling the open physiological-pH structure and a closed conformation that displays six threads of density, that join to form a pore-occluding density. Crosslinking and hydrogen-deuterium exchange mass spectrometry reveal closer association between the N-terminal (NT) domains and the cytoplasmic loops (CL) at acidic pH. Previous electrophysiologic studies suggest an association between NT residue N14 and H100 near M2, which may trigger the observed movement of M2 toward M1 in our cryo-EM maps, thereby accounting for additional NT-CL crosslinks at acidic pH. We propose that these pH-induced interactions and conformational changes result in extension, ordering, and association of the acetylated NT domains to form a hexameric "ball-and-chain" gating particle.

PubMed: 32320665
DOI: 10.1016/j.celrep.2020.03.046

実験手法

ELECTRON MICROSCOPY (4 Å)