7Z14
Cryo-EM structure of Torpedo nicotinic acetylcholine receptor in complex with a short-chain neurotoxin.
Summary for 7Z14
| Entry DOI | 10.2210/pdb7z14/pdb |
| EMDB information | 14440 |
| Descriptor | Acetylcholine receptor subunit alpha, Acetylcholine receptor subunit beta, Acetylcholine receptor subunit delta, ... (9 entities in total) |
| Functional Keywords | ion channel, toxin, membrane protein |
| Biological source | synthetic construct More |
| Total number of polymer chains | 7 |
| Total formula weight | 286868.07 |
| Authors | Nys, M.A.E.M.,Zarkadas, E.,Ulens, C.,Nury, H. (deposition date: 2022-02-24, release date: 2022-08-17, Last modification date: 2022-08-24) |
| Primary citation | Nys, M.,Zarkadas, E.,Brams, M.,Mehregan, A.,Kambara, K.,Kool, J.,Casewell, N.R.,Bertrand, D.,Baenziger, J.E.,Nury, H.,Ulens, C. The molecular mechanism of snake short-chain alpha-neurotoxin binding to muscle-type nicotinic acetylcholine receptors. Nat Commun, 13:4543-4543, 2022 Cited by PubMed Abstract: 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. PubMed: 35927270DOI: 10.1038/s41467-022-32174-7 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.15 Å) |
Structure validation
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