9ney

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

spinqualitylabelsall models 9ney, resolution 3.06Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9ney is a 3 chain structure with sequence from Clostridium botulinum and Homo sapiens. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 3.06Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function BXA1_CLOBO Inhibits acetylcholine release. The botulinum toxin binds with high affinity to peripheral neuronal presynaptic membrane to the secretory vesicle protein SV2. It binds directly to the largest luminal loop of SV2A, SV2B and SV2C. It is then internalized by receptor-mediated endocytosis. The C-terminus of the heavy chain (H) is responsible for the adherence of the toxin to the cell surface while the N-terminus mediates transport of the light chain from the endocytic vesicle to the cytosol. After translocation, the light chain (L) hydrolyzes the 197-Gln-|-Arg-198 bond in SNAP-25, thereby blocking neurotransmitter release. Inhibition of acetylcholine release results in flaccid paralysis, with frequent heart or respiratory failure. Publication Abstract from PubMed 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. A belt-buckle checkpoint regulates the onset of botulinum neurotoxin intoxication.,Chen B, Gao L, Bonninger M, Huang T, Krez N, Wen W, Bowen M, Lou J, Marks JD, Rummel A, Jin R Nat Commun. 2026 Jun 23;17(1):5562. doi: 10.1038/s41467-026-74499-7. PMID:42337249 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

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