Cocrystal structure of synaptobrevin-II bound to botulinum neurotoxin typeB at 2.0 angstrom resolution

Botulinum neurotoxin serotype B is a zinc protease that disrupts neurotrans mitter release by cleaving synaptobrevin-II (Sb2), one of three SNARE prote ins involved in neuronal synaptic vesicle fusion. The three-dimensional cry stal structure of the apo botulinum neurotoxin serotype B catalytic domain (BoNT/B-LC) has been determined to 2.2 Angstrom resolution, and the complex of cleaved Sb2 with the catalytic domain (Sb2-BoNT/B-LC) has been determin ed to 2.0 Angstrom resolution. A comparison of the holotoxin catalytic doma in and the isolated BoNT/B-LC structure shows a rearrangement of three acti ve site loops. This rearrangement exposes the BoNT/B active site. The Sb2-B oNT/B-LC structure illustrates two distinct binding regions, which explains the specificity of each botulinum neurotoxin for its synaptic vesicle prot ein. This observation provides an explanation for the proposed cooperativit y between binding of full-length substrate and catalysis and suggest a mech anism of synaptobrevin proteolysis employed by the clostridial neurotoxins.