8QA2

Cryo-EM structure of Cx26 solubilised in LMNG: classification on subunit A; Nconst-mon conformation

8QA2 の概要

• エントリーDOI: 10.2210/pdb8qa2/pdb
• EMDBエントリー: 18293
• 分子名称: Gap junction beta-2 protein, PHOSPHATIDYLETHANOLAMINE (3 entities in total)
• 機能のキーワード: gap junction large pore channel carbon dioxide sensitive, 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: 330106.59

構造登録者

Brotherton, D.H.,Cameron, A.D. (登録日: 2023-08-22, 公開日: 2024-06-12, 最終更新日: 2024-11-20)

主引用文献

Brotherton, D.H.,Nijjar, S.,Savva, C.G.,Dale, N.,Cameron, A.D.
Structures of wild-type and a constitutively closed mutant of connexin26 shed light on channel regulation by CO 2.
Elife, 13:-, 2024

PubMed Abstract: Connexins allow intercellular communication by forming gap junction channels (GJCs) between juxtaposed cells. Connexin26 (Cx26) can be regulated directly by CO. This is proposed to be mediated through carbamylation of K125. We show that mutating K125 to glutamate, mimicking the negative charge of carbamylation, causes Cx26 GJCs to be constitutively closed. Through cryo-EM we observe that the K125E mutation pushes a conformational equilibrium towards the channel having a constricted pore entrance, similar to effects seen on raising the partial pressure of CO. In previous structures of connexins, the cytoplasmic loop, important in regulation and where K125 is located, is disordered. Through further cryo-EM studies we trap distinct states of Cx26 and observe density for the cytoplasmic loop. The interplay between the position of this loop, the conformations of the transmembrane helices and the position of the N-terminal helix, which controls the aperture to the pore, provides a mechanism for regulation.

PubMed: 38829031
DOI: 10.7554/eLife.93686

実験手法

ELECTRON MICROSCOPY (2.3 Å)