Structural highlights
FunctionACHA_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 PubMedBites 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 AlsoReferences
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