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9CZB

CryoEM structure of BoNT/E at pH5, class 1

Summary for 9CZB
Entry DOI10.2210/pdb9czb/pdb
EMDB information46409
DescriptorBont/E (1 entity in total)
Functional Keywordsbotulinum neurotoxin, toxin
Biological sourceClostridium botulinum
Total number of polymer chains1
Total formula weight143587.94
Authors
Gao, L. (deposition date: 2024-08-05, release date: 2026-07-22)
Primary citationChen, 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
Cited by
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
PDB entries with the same primary citation
Experimental method
ELECTRON MICROSCOPY (3.7 Å)
Structure validation

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