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TitleThe molecular mechanism of snake short-chain α-neurotoxin binding to muscle-type nicotinic acetylcholine receptors.
Journal, issue, pagesNat Commun, Vol. 13, Issue 1, Page 4543, Year 2022
Publish dateAug 4, 2022
AuthorsMieke Nys / Eleftherios Zarkadas / Marijke Brams / Aujan Mehregan / Kumiko Kambara / Jeroen Kool / Nicholas R Casewell / Daniel Bertrand / John E Baenziger / Hugues Nury / Chris Ulens /
PubMed AbstractBites by elapid snakes (e.g. cobras) can result in life-threatening paralysis caused by venom neurotoxins blocking neuromuscular nicotinic acetylcholine receptors. Here, we determine the cryo-EM ...Bites by elapid snakes (e.g. cobras) can result in life-threatening paralysis caused by venom neurotoxins blocking neuromuscular nicotinic acetylcholine receptors. Here, we determine the cryo-EM structure of the muscle-type Torpedo receptor in complex with ScNtx, a recombinant short-chain α-neurotoxin. ScNtx is pinched between loop C on the principal subunit and a unique hairpin in loop F on the complementary subunit, thereby blocking access to the neurotransmitter binding site. ScNtx adopts a binding mode that is tilted toward the complementary subunit, forming a wider network of interactions than those seen in the long-chain α-Bungarotoxin complex. Certain mutations in ScNtx at the toxin-receptor interface eliminate inhibition of neuronal α7 nAChRs, but not of human muscle-type receptors. These observations explain why ScNtx binds more tightly to muscle-type receptors than neuronal receptors. Together, these data offer a framework for understanding subtype-specific actions of short-chain α-neurotoxins and inspire strategies for design of new snake antivenoms.
External linksNat Commun / PubMed:35927270 / PubMed Central
MethodsEM (single particle)
Resolution3.15 Å
Structure data

14440

7z14

EMDB-14440, PDB-7z14:
Cryo-EM structure of Torpedo nicotinic acetylcholine receptor in complex with a short-chain neurotoxin.
Method: EM (single particle) / Resolution: 3.15 Å

Chemicals

ChemComp-NAG:
2-acetamido-2-deoxy-beta-D-glucopyranose

Source
  • Pacific electric ray (Pacific electric ray)
  • synthetic construct (others)
  • tetronarce californica (Pacific electric ray)
KeywordsMEMBRANE PROTEIN / Ion channel / toxin

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