8XGF

Human Cx36/GJD2 gap junction channel in complex with arachidonic acid.

8XGF の概要

• エントリーDOI: 10.2210/pdb8xgf/pdb
• EMDBエントリー: 33255 33327 38320
• 分子名称: Gap junction delta-2 protein, 1,2-DIMYRISTOYL-RAC-GLYCERO-3-PHOSPHOCHOLINE, ARACHIDONIC ACID (3 entities in total)
• 機能のキーワード: connexin 36, gap junction channel, cx36, gjd2, membrane protein, arachidonic acid
• 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: 509122.90

構造登録者

Cho, H.J.,Lee, H.H. (登録日: 2023-12-15, 公開日: 2024-11-06, 最終更新日: 2025-07-02)

主引用文献

Cho, H.J.,Chung, D.K.,Lee, H.H.
Mefloquine-induced conformational shift in Cx36 N-terminal helix leading to channel closure mediated by lipid bilayer.
Nat Commun, 15:9223-9223, 2024

PubMed Abstract: Connexin 36 (Cx36) forms interneuronal gap junctions, establishing electrical synapses for rapid synaptic transmission. In disease conditions, inhibiting Cx36 gap junction channels (GJCs) is beneficial, as it prevents abnormal synchronous neuronal firing and apoptotic signal propagation, mitigating seizures and progressive cell death. Here, we present cryo-electron microscopy structures of human Cx36 GJC in complex with known channel inhibitors, such as mefloquine, arachidonic acid, and 1-hexanol. Notably, these inhibitors competitively bind to the binding pocket of the N-terminal helices (NTH), inducing a conformational shift from the pore-lining NTH (PLN) state to the flexible NTH (FN) state. This leads to the obstruction of the channel pore by flat double-layer densities of lipids. These studies elucidate the molecular mechanisms of how Cx36 GJC can be modulated by inhibitors, providing valuable insights into potential therapeutic applications.

PubMed: 39455592
DOI: 10.1038/s41467-024-53587-6

実験手法

ELECTRON MICROSCOPY (2.95 Å)