Membrane-mediated interaction of non-conventional snake three-finger toxins with nicotinic acetylcholine receptors.
Journal
Communications biology
ISSN: 2399-3642
Titre abrégé: Commun Biol
Pays: England
ID NLM: 101719179
Informations de publication
Date de publication:
07 12 2022
07 12 2022
Historique:
received:
07
12
2021
accepted:
28
11
2022
entrez:
8
12
2022
pubmed:
9
12
2022
medline:
15
12
2022
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 36477694
doi: 10.1038/s42003-022-04308-6
pii: 10.1038/s42003-022-04308-6
pmc: PMC9729238
doi:
Substances chimiques
Receptors, Nicotinic
0
Three Finger Toxins
0
Bungarotoxins
0
Neurotoxins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1344Informations de copyright
© 2022. The Author(s).
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