9VIX

human alpha 7 nicotinic acetylcholine receptor L278A mutant in complex with L-nicotine (desensitized state)

9VIX の概要

• エントリーDOI: 10.2210/pdb9vix/pdb
• EMDBエントリー: 65097
• 分子名称: Neuronal acetylcholine receptor subunit alpha-7, 2-acetamido-2-deoxy-beta-D-glucopyranose-(1-4)-2-acetamido-2-deoxy-beta-D-glucopyranose, (S)-3-(1-METHYLPYRROLIDIN-2-YL)PYRIDINE, ... (5 entities in total)
• 機能のキーワード: ligand-gated ion channel, nicotine, desensitization, recovery, closed pore, membrane protein, mutant
• 由来する生物種: Homo sapiens (human)
• タンパク質・核酸の鎖数: 5
• 化学式量合計: 291910.06

構造登録者

Liu, S.,Chen, H.,Tian, C. (登録日: 2025-06-19, 公開日: 2025-09-10, 最終更新日: 2025-10-29)

主引用文献

Liu, S.,Chen, H.,Zhu, X.,Ye, F.,Zhao, Y.,Qin, J.,Zheng, Y.,Wang, X.,Zhang, L.,Chen, H.,Li, X.,Mu, W.,Fu, Y.,Luo, C.,Hou, H.,Bai, C.,Liu, L.,Tian, C.
Structural insights into the progressive recovery of alpha 7 nicotinic acetylcholine receptor from nicotine-induced desensitization.
Sci Adv, 11:eadx4432-eadx4432, 2025

PubMed Abstract: Nicotine is the predominant alkaloid in tobacco leaves and affects the human nervous system by interacting with nicotinic acetylcholine receptors (nAChRs). Chronic nicotine exposure leads to nAChR desensitization, while nicotine withdrawal leads to nAChR recovery. However, detailed molecular mechanisms underlying nicotine-induced nAChR desensitization and its recovery remain elusive. Here, we present cryo-EM structures of the α7 nAChR in complex with nicotine in both an open state and multiple desensitized states. Comparative analyses reveal progressive conformational changes during recovery from nicotine-induced desensitization and show that asymmetric nicotine binding disrupts the symmetry of the channel pore at the 16' and 17' sites. Integrating these findings with patch-clamp recordings and computational simulations, we identify an agonist-free structure that represents an atypical desensitized state closely resembling the resting conformation of α7 nAChR. These detailed mechanistic studies enhance our understanding of nicotine's effects on α7 nAChRs.

PubMed: 41071887
DOI: 10.1126/sciadv.adx4432

実験手法

ELECTRON MICROSCOPY (3.06 Å)