9Z9Y

Gated state sheep connexin-50 in DMPC nanodiscs at low pH

9Z9Y の概要

• エントリーDOI: 10.2210/pdb9z9y/pdb
• 関連するPDBエントリー: 9Z7P 9Z7W 9Z81 9Z82 9Z8F 9Z8L 9Z8M 9Z9B 9Z9G 9Z9H 9Z9S 9Z9W 9Z9X
• EMDBエントリー: 7396
• 分子名称: Gap junction alpha-8 protein, 1,2-DIMYRISTOYL-RAC-GLYCERO-3-PHOSPHOCHOLINE (3 entities in total)
• 機能のキーワード: connexin, gap junction, cryo-em, ph regulation, lipid gating, large-pore channel, membrane protein
• 由来する生物種: Ovis aries (sheep)
• タンパク質・核酸の鎖数: 12
• 化学式量合計: 859063.18

構造登録者

Jarodsky, J.M.,Myers, J.B.,Reichow, S.L. (登録日: 2025-11-18, 公開日: 2026-01-28, 最終更新日: 2026-02-25)

主引用文献

Jarodsky, J.M.,Myers, J.B.,Reichow, S.L.
Reversible lipid-mediated pH-gating of connexin-46/50 by cryo-EM.
Nat Commun, 17:1606-1606, 2026

PubMed Abstract: Gap junctions, formed by connexin proteins, establish direct electrical and metabolic coupling between cells, enabling coordinated tissue responses. These channels universally respond to intracellular pH changes, closing under acidic conditions to limit the spread of cytotoxic signals during cellular stress, such as ischemia. Using cryo-electron microscopy (cryo-EM), we uncover insights into the structural mechanism of pH-gating in native lens connexin-46/50 (Cx46/50) gap junctions. Mild acidification drives lipid infiltration into the channel pore, displacing the N-terminal (NT) domain and stabilizing pore closure. Lipid involvement is shown to be both essential and fully reversible. Structural transitions involve an ensemble of gated states formed through non-cooperative NT domain movement as well as minor populations of a distinct destabilized open-state. These findings provide molecular insights into pH-gating dynamics, illustrating how structural changes may regulate gap junction function under cellular stress and linking Cx46/50 dysregulation to age-related cataract formation.

PubMed: 41526355
DOI: 10.1038/s41467-026-68311-9

実験手法

ELECTRON MICROSCOPY (2.3 Å)