9NEY
The structure of BoNT/A in complex with a neutralizing antibody 2G11
Summary for 9NEY
| Entry DOI | 10.2210/pdb9ney/pdb |
| EMDB information | 49339 |
| Descriptor | Botulinum neurotoxin type A, Heavy Chain, Light Chain (3 entities in total) |
| Functional Keywords | bont, antibody, immune system-toxin complex, immune system/toxin |
| Biological source | Clostridium botulinum More |
| Total number of polymer chains | 3 |
| Total formula weight | 196760.48 |
| Authors | |
| Primary citation | 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 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: 42337249DOI: 10.1038/s41467-026-74499-7 PDB entries with the same primary citation |
| Experimental method | ELECTRON MICROSCOPY (3.06 Å) |
Structure validation
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