9czb | pdb_00009czb

CryoEM structure of BoNT/E at pH5, class 1

spinqualitylabelsall models 9czb, resolution 3.70Å Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 9czb is a 1 chain structure with sequence from Clostridium botulinum. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance. Method: Electron Microscopy, Resolution 3.7Å Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function Q54A79_CLOBO 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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