Structural basis for recognition of synaptic vesicle protein 2C by botulinum neurotoxin A

Botulinum neurotoxin A (BoNT/A) is at the same time one of the most dangerous of bioweapons and, as botox, is familiar to all as an antiwrinkle agent. The toxin acts by inhibiting neurotransmitter release through cleavage of SNAP-25, and this study presents the high-resolution crystal structure of the BoNT/A receptor-binding domain in complex with the luminal domain of synaptic vesicle protein 2C (SV2C), one of the receptors for BoNT/A. The structure indicates that SV2C forms a right-handed quadrilateral -helix that associates with the toxin mainly via backbonebackbone interactions, reminiscent of the interstrand interactions seen in amyloid structures. The authors also identify a peptide that can act as an inhibitor of complex formation, suggesting a possible route to novel antitoxin agents.