Ternary SNARE complexes

The LC then targets and cleaves one or more of three soluble NSF attachment protein receptor (SNARE) proteins with exquisite specificity synaptosomal-associated protein 25 (SNAP-25 BoNT/A, /C, /E) vesicle associated membrane protein 1-3 (VAMPl-3 BoNT-/B, /D, /F, /G) or syntaxin (BoNT/C). The SNARE proteins are essential components of the synaptic exocytosis mechanism, and their cleavage prevents functional assembly of the ternary complex, thereby blocking neurotransmitter release. The combination of efficient neuronal targeting and presynaptic activation renders BoNTs the most potent substances known, with estimated human lethal doses as low as 0.1-1 ng/kg. 

Fig. 6.4 Model for protein-mediated membrane fusion and exocytosis. a The release of acetylcholine from the vesicles is mediated by a series of proteins collectively called SNARE proteins. Synaptotagmin is the neuronal Ca " receptor detecting C entry. Synaptobrevin (i.e. vesicle-associated membrane protein, VAMP) is a filament-like protein on the vesicle, b During depolarisation and calcium entry, synaptobrevin on the vesicle unfolds and forms a ternary complex with syntaxin/SNAP-25. This process is facilitated by phosphorylation of synapsin, also present on the vesicle membrane, c Assembly of the ternary complex forces the vesicle in close apposition to the nerve membrane at the active zone with release of its contents, acetylcholine. The fusion is disassembled, and the vesicle is recycled. (From Martyn 2005, p 864 copyright Elsevier)...

---