Identification of the nerve terminal targets of botulinum neurotoxin serotypes A, D, and E.
- G Schiavo,
- O Rossetto,
- S Catsicas,
- P Polverino de Laureto,
- B R DasGupta,
- F Benfenati and
- C Montecucco
Abstract
Botulinum neurotoxins are metalloproteins with one zinc atom bound to the zinc binding motif of zinc endopeptidases. Here we show that botulinum neurotoxin serotypes A, D, and E are zinc endoproteases specific for components of the synaptic vesicle docking and fusion complex. Serotypes A and E cleave SNAP-25, a 25-kDa protein of the synaptic terminal, while serotype D is specific for VAMP/synaptobrevin, a membrane protein of synaptic vesicles. Both rat brain VAMP isoforms are cleaved at a single Lys-Leu peptide bond. The proteolytic activity of these neurotoxins is inhibited by EDTA and captopril.
