9Z7P

Stable open sheep connexin-46 in amphipol at low pH

9Z7P の概要

• エントリーDOI: 10.2210/pdb9z7p/pdb
• EMDBエントリー: 73876
• 分子名称: Gap junction alpha-3 protein (1 entity 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: 528396.32

構造登録者

Jarodsky, J.M.,Myers, J.B.,Reichow, S.L. (登録日: 2025-11-17, 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 (2.7 Å)