7Z14

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

7Z14 の概要

• エントリーDOI: 10.2210/pdb7z14/pdb
• EMDBエントリー: 14440
• 分子名称: Acetylcholine receptor subunit alpha, Acetylcholine receptor subunit beta, Acetylcholine receptor subunit delta, ... (9 entities in total)
• 機能のキーワード: ion channel, toxin, membrane protein
• 由来する生物種: synthetic construct; 詳細
• タンパク質・核酸の鎖数: 7
• 化学式量合計: 286868.07

構造登録者

Nys, M.A.E.M.,Zarkadas, E.,Ulens, C.,Nury, H. (登録日: 2022-02-24, 公開日: 2022-08-17, 最終更新日: 2024-11-06)

主引用文献

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

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: 35927270
DOI: 10.1038/s41467-022-32174-7

実験手法

ELECTRON MICROSCOPY (3.15 Å)