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TitleA belt-buckle checkpoint regulates the onset of botulinum neurotoxin intoxication.
Journal, issue, pagesNat Commun, Vol. 17, Issue 1, Year 2026
Publish dateJun 23, 2026
AuthorsBaohua Chen / Linfeng Gao / Melvin Bönninger / Ting Huang / Nadja Krez / Weihua Wen / Mark Bowen / Jianlong Lou / James D Marks / Andreas Rummel / Rongsheng Jin /
PubMed AbstractFast-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, ...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.
External linksNat Commun / PubMed:42337249 / PubMed Central
MethodsEM (single particle)
Resolution3.06 - 11.0 Å
Structure data

EMDB-46803: CryoEM structure of BoNT/E at pH5, class 5, BoNT/A-like
Method: EM (single particle) / Resolution: 11.0 Å

49339

9ney

EMDB-49339, PDB-9ney:
The structure of BoNT/A in complex with a neutralizing antibody 2G11
Method: EM (single particle) / Resolution: 3.06 Å

EMDB-76739: The density map of BoNT/A mutant (BoNT/A-WFY)
Method: EM (single particle) / Resolution: 7.51 Å

Source
  • Clostridium botulinum E1 str. 'BoNT E Beluga' (bacteria)
  • clostridium botulinum (bacteria)
  • homo sapiens (human)
KeywordsIMMUNE SYSTEM/TOXIN / BoNT / antibody / IMMUNE SYSTEM-TOXIN complex

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