8ZRN

Structure of abt

これはPDB形式変換不可エントリーです。

8ZRN の概要

• エントリーDOI: 10.2210/pdb8zrn/pdb
• EMDBエントリー: 60400
• 分子名称: Neuronal acetylcholine receptor subunit alpha-6, Neuronal acetylcholine receptor subunit beta-4,Soluble cytochrome b562, beta-D-mannopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, ... (5 entities in total)
• 機能のキーワード: abt-bound, membrane protein
• 由来する生物種: Homo sapiens (human); 詳細
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 331276.81

構造登録者

Su, J.,Yu, Z.,Zhao, Y. (登録日: 2024-06-04, 公開日: 2025-04-30, 最終更新日: 2025-07-16)

主引用文献

Su, J.,Yu, Z.,Yin, Z.,Zhang, Z.,Zhao, J.,Meng, Y.,Li, R.,Gao, Y.,Zhang, H.,Yu, R.,Zhao, Y.
Molecular insights into the alpha 6 beta 4 nicotinic acetylcholine receptor function and ligand recognition.
Nat Commun, 16:3153-3153, 2025

PubMed Abstract: The α6β4 nicotinic acetylcholine receptor (nAChR) is found in the sensory neurons of dorsal root ganglia. It is a promising therapeutic target for pain. However, the difficultly of heterologous functional expression of α6β4 receptor has hindered the discovery of drugs that target it. Here, we functionally express the human α6β4 receptor and determine the cryo-EM structures of α6β4 receptor in complex with its agonists, nicotine and the preclinical drug tebanicline. These structures were captured in non-conducting desensitized states. We elucidate that the stoichiometry of α- and β- subunits in the α6β4 receptor is 2α6:3β4. Furthermore, we identify the binding pockets for nicotine and tebanicline, demonstrating the essential residues contributing to ligand affinity and providing detailed molecular insights into why these agonists have different binding affinities despite both occupying the orthosteric site of the α6β4 receptor. These structures offer significant molecular insight into the function and ligand recognition of α6β4 receptor.

PubMed: 40175361
DOI: 10.1038/s41467-025-58333-0

実験手法

ELECTRON MICROSCOPY (3.25 Å)