Botulinum toxin mode of action

Botulinum toxin is expressed as an inactive 150 kDa polypeptide comprising a 100kDa heavy chain (HC) and a 50 kDa light chain (LC) linked through a disulphide bridge. HC binds the toxin to the presynaptic receptor; toxin enters the cell & the disulphide bond is cleaved. Cleavage liberates the LC into the cytoplasm and endosomal compartment. LC acts as a zinc endopeptidase, cleaving the synaptosomal-associated protein (SNAP), vesicle-associated membrane protein (VAMP) and syntaxin. This prevents fusion of acetylcholine vesicles at the cell membrane.