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-Structure paper
タイトル | The molecular mechanism of snake short-chain α-neurotoxin binding to muscle-type nicotinic acetylcholine receptors. |
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ジャーナル・号・ページ | Nat Commun, Vol. 13, Issue 1, Page 4543, Year 2022 |
掲載日 | 2022年8月4日 |
著者 | Mieke Nys / Eleftherios Zarkadas / Marijke Brams / Aujan Mehregan / Kumiko Kambara / Jeroen Kool / Nicholas R Casewell / Daniel Bertrand / John E Baenziger / Hugues Nury / Chris Ulens / |
PubMed 要旨 | 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 ...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. |
リンク | Nat Commun / PubMed:35927270 / PubMed Central |
手法 | EM (単粒子) |
解像度 | 3.15 Å |
構造データ | EMDB-14440, PDB-7z14: |
化合物 | ChemComp-NAG: |
由来 |
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キーワード | MEMBRANE PROTEIN / Ion channel / toxin |