9NEY

The structure of BoNT/A in complex with a neutralizing antibody 2G11

9NEY の概要

• エントリーDOI: 10.2210/pdb9ney/pdb
• EMDBエントリー: 49339
• 分子名称: Botulinum neurotoxin type A, Heavy Chain, Light Chain (3 entities in total)
• 機能のキーワード: bont, antibody, immune system-toxin complex, immune system/toxin
• 由来する生物種: Clostridium botulinum; 詳細
• タンパク質・核酸の鎖数: 3
• 化学式量合計: 196760.48

構造登録者

Chen, B.,Jin, R. (登録日: 2025-02-20, 公開日: 2026-07-01)

主引用文献

Chen, B.,Gao, L.,Bonninger, M.,Huang, T.,Krez, N.,Wen, W.,Bowen, M.,Lou, J.,Marks, J.D.,Rummel, A.,Jin, R.
A belt-buckle checkpoint regulates the onset of botulinum neurotoxin intoxication.
Nat Commun, 17:-, 2026

PubMed Abstract: Fast-acting botulinum neurotoxins (BoNTs) are highly desirable for both medical and aesthetic indications, but the underlying mechanism for the differing onset of BoNTs' action remains unknown. Here, we demonstrate that the "belt" of BoNTs, a largely unstructured loop wrapping around their catalytic light chain (LC), is key to onset of intoxication. The more flexible BoNT/E belt promotes quicker LC translocation into the neuronal cytosol, leading to faster onset of action compared to BoNT/A. Furthermore, we discover a "belt-buckle" checkpoint that regulates this process. By loosening the BoNT/A belt-buckle via protein engineering, we enhance its sensitivity to acidic pH, leading to an accelerated onset of action. Conversely, locking the belt-buckle with an antibody neutralizes BoNT/A. Our findings open avenues for developing fast-acting BoNTs and effective countermeasures.

PubMed: 42337249
DOI: 10.1038/s41467-026-74499-7

実験手法

ELECTRON MICROSCOPY (3.06 Å)