EMDB/PDB/SASBDBから引用されている文献のデータベース

キーワード
構造解析手法	All X線回折 NMR 電子顕微鏡小角散乱中性子線回折線維回折粉末回折赤外分光 EPR FRET 理論モデルハイブリッド
著者・登録者
ジャーナル
IF	>30 >20 >10 >5 all

タイトル	Structural insights into the progressive recovery of α7 nicotinic acetylcholine receptor from nicotine-induced desensitization.
ジャーナル・号・ページ	Sci Adv, Vol. 11, Issue 41, Page eadx4432, Year 2025
掲載日	2025年10月10日
著者	Sanling Liu / Haopeng Chen / Xiaohong Zhu / Fei Ye / Yue Zhao / Junlin Qin / Yining Zheng / Xudong Wang / Longhua Zhang / Huan Chen / Xin Li / Wenjun Mu / Yaning Fu / Cheng Luo / Hongwei Hou / Chen Bai / Lei Liu / Changlin Tian /
PubMed 要旨	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 ...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.
リンク	Sci Adv / PubMed:41071887 / PubMed Central
手法	EM (単粒子)
解像度	2.61 - 3.25 Å
構造データ	63084 9lh5 EMDB-63084, PDB-9lh5: human alpha 7 nicotinic acetylcholine receptor in complex with L-nicotine (open state) 手法: EM (単粒子) / 解像度: 2.61 Å 63086 9lh6 EMDB-63086, PDB-9lh6: human alpha 7 nicotinic acetylcholine receptor in complex with L-nicotine (five-nicotine-bound desensitized state) 手法: EM (単粒子) / 解像度: 2.69 Å 63089 9lh8 EMDB-63089, PDB-9lh8: human alpha 7 nicotinic acetylcholine receptor in complex with L-nicotine (four-nicotine-bound desensitized state) 手法: EM (単粒子) / 解像度: 2.74 Å 63090 9lh9 EMDB-63090, PDB-9lh9: human alpha 7 nicotinic acetylcholine receptor in complex with L-nicotine (ortho-three-nicotine-bound desensitized state) 手法: EM (単粒子) / 解像度: 2.98 Å 63091 9lha EMDB-63091, PDB-9lha: human alpha 7 nicotinic acetylcholine receptor in complex with L-nicotine (meta-three-nicotine-bound desensitized state) 手法: EM (単粒子) / 解像度: 2.96 Å 63092 9lhb EMDB-63092, PDB-9lhb: human alpha 7 nicotinic acetylcholine receptor in complex with L-nicotine (ortho-two-nicotine-bound desensitized state) 手法: EM (単粒子) / 解像度: 3.11 Å 63093 9lhc EMDB-63093, PDB-9lhc: human alpha 7 nicotinic acetylcholine receptor in complex with L-nicotine (meta-two-nicotine-bound desensitized state) 手法: EM (単粒子) / 解像度: 3.17 Å 63094 9lhd EMDB-63094, PDB-9lhd: human alpha 7 nicotinic acetylcholine receptor in complex with L-nicotine (one-nicotine-bound desensitized state) 手法: EM (単粒子) / 解像度: 3.24 Å 63095 9lhe EMDB-63095, PDB-9lhe: human alpha 7 nicotinic acetylcholine receptor in complex with L-nicotine (nicotine-free desensitized state) 手法: EM (単粒子) / 解像度: 3.25 Å 65096 9viq EMDB-65096, PDB-9viq: human alpha 7 nicotinic acetylcholine receptor L277A mutant in complex with L-nicotine (desensitized state) 手法: EM (単粒子) / 解像度: 3.24 Å 65097 9vix EMDB-65097, PDB-9vix: human alpha 7 nicotinic acetylcholine receptor L278A mutant in complex with L-nicotine (desensitized state) 手法: EM (単粒子) / 解像度: 3.06 Å
化合物	ChemComp-NCT: (S)-3-(1-METHYLPYRROLIDIN-2-YL)PYRIDINE / 3-[(1R)-1β-メチルピロリジン-2α-イル]ピリジン / alkaloidYM ChemComp-NAG: 2-acetamido-2-deoxy-beta-D-glucopyranose / N-アセチル-β-D-グルコサミン ChemComp-HOH*: WATER
由来	homo sapiens (ヒト)
キーワード	MEMBRANE PROTEIN / Ligand-gated ion channel / Nicotine / Desensitization / Recovery / Open pore / Closed pore / mutant