Cryo-EM structure of Torpedo nicotinic acetylcholine receptor in complex with a short-chain neurotoxin.Cryo-EM structure of Torpedo nicotinic acetylcholine receptor in complex with a short-chain neurotoxin.

Structural highlights

7z14 is a 7 chain structure with sequence from Tetronarce californica and Synthetic construct. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Method:Electron Microscopy, Resolution 3.15Å
Ligands:, ,
Resources:FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Function

ACHA_TETCF After binding acetylcholine, the AChR responds by an extensive change in conformation that affects all subunits and leads to opening of an ion-conducting channel across the plasma membrane.

Publication Abstract from PubMed

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 alpha-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 alpha-Bungarotoxin complex. Certain mutations in ScNtx at the toxin-receptor interface eliminate inhibition of neuronal alpha7 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 alpha-neurotoxins and inspire strategies for design of new snake antivenoms.

The molecular mechanism of snake short-chain alpha-neurotoxin binding to muscle-type nicotinic acetylcholine receptors.,Nys M, Zarkadas E, Brams M, Mehregan A, Kambara K, Kool J, Casewell NR, Bertrand D, Baenziger JE, Nury H, Ulens C Nat Commun. 2022 Aug 4;13(1):4543. doi: 10.1038/s41467-022-32174-7. PMID:35927270[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

See Also

References

  1. Nys M, Zarkadas E, Brams M, Mehregan A, Kambara K, Kool J, Casewell NR, Bertrand D, Baenziger JE, Nury H, Ulens C. The molecular mechanism of snake short-chain α-neurotoxin binding to muscle-type nicotinic acetylcholine receptors. Nat Commun. 2022 Aug 4;13(1):4543. PMID:35927270 doi:10.1038/s41467-022-32174-7

7z14, resolution 3.15Å

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