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-Structure paper
タイトル | Membrane-mediated interaction of non-conventional snake three-finger toxins with nicotinic acetylcholine receptors. |
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ジャーナル・号・ページ | Commun Biol, Vol. 5, Issue 1, Page 1344, Year 2022 |
掲載日 | 2022年12月7日 |
![]() | Zakhar O Shenkarev / Yuri M Chesnokov / Maxim M Zaigraev / Anton O Chugunov / Dmitrii S Kulbatskii / Milita V Kocharovskaya / Alexander S Paramonov / Maxim L Bychkov / Mikhail A Shulepko / Dmitry E Nolde / Roman A Kamyshinsky / Evgeniy O Yablokov / Alexey S Ivanov / Mikhail P Kirpichnikov / Ekaterina N Lyukmanova / ![]() |
PubMed 要旨 | Nicotinic acetylcholine receptor of α7 type (α7-nAChR) presented in the nervous and immune systems and epithelium is a promising therapeutic target for cognitive disfunctions and cancer treatment. ...Nicotinic acetylcholine receptor of α7 type (α7-nAChR) presented in the nervous and immune systems and epithelium is a promising therapeutic target for cognitive disfunctions and cancer treatment. Weak toxin from Naja kaouthia venom (WTX) is a non-conventional three-finger neurotoxin, targeting α7-nAChR with weak affinity. There are no data on interaction mode of non-conventional neurotoxins with nAChRs. Using α-bungarotoxin (classical three-finger neurotoxin with high affinity to α7-nAChR), we showed applicability of cryo-EM to study complexes of α7-nAChR extracellular ligand-binding domain (α7-ECD) with toxins. Using cryo-EM structure of the α7-ECD/WTX complex, together with NMR data on membrane active site in the WTX molecule and mutagenesis data, we reconstruct the structure of α7-nAChR/WTX complex in the membrane environment. WTX interacts at the entrance to the orthosteric site located at the receptor intersubunit interface and simultaneously forms the contacts with the membrane surface. WTX interaction mode with α7-nAChR significantly differs from α-bungarotoxin's one, which does not contact the membrane. Our study reveals the important role of the membrane for interaction of non-conventional neurotoxins with the nicotinic receptors. |
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手法 | EM (単粒子) |
解像度 | 3.37 - 6.6 Å |
構造データ | ![]() EMDB-16169: Alpha7-nAChR extracellular ligand-binding domain (alpha7-ECD)in complex with alpha-bungarotoxin. ![]() EMDB-16173: Alpha7-nAChR extracellular ligand-binding domain (alpha7-ECD)in complex with a weak neurotoxin WTX. |
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