New insights into clostridial neurotoxin-SNARE interactions

Abstract

Botulinum neurotoxin serotype A (BoNT/A) has achieved a dichotomous status in modern medicine; it is both a versatile treatment for several neurological disorders and a lethal poison responsible for causing the neuroparalytic syndrome botulism. The extent of paralysis largely depends on the dosage of toxin received. The toxins block neurotransmitter release by delivering their Zn(2+)-dependent protease components to the presynaptic side of chemical synapses. These highly specialized enzymes exclusively hydrolyze peptide bonds within SNARE (soluble N-ethylmaleiamide-sensitive factor attachment protein receptor) proteins. Recently, the structural basis for the highly specific interaction between BoNT/A and its target SNARE, SNAP-25 (synaptosomal-associated protein of 25kDa), was elucidated. New details regarding the nature of the toxin-SNARE interactions could be exploited for novel inhibitor design.