BOTULINUM NEUROTOXIN TYPE-G PROTEOLYSES THE ALA(81)-ALA(82) BOND OF RAT SYNAPTOBREVIN-2

Tetanus toxin and the botulinum neurotoxins types A to F inhibit neuro transmitter release from presynaptic nerve endings by selectively prot eolysing the synaptic proteins synaptobrevin, syntaxin, or SNAP-25. He re, we show that botulinum toxin type G cleaves rat synaptobrevin 2 be tween Ala(81) and Ala(82), a peptide bond that differs from those atta cked by tetanus toxin and the botulinal toxins types B, D, and F. Syna ptobrevin isoforms carrying a Gly in the P1 position are poor substrat es. Analyses of N-terminal deletion mutants of rat synaptobrevin 2 sho wed that a substrate starting at Leu(54) is cleaved efficiently, where as substrates beginning at Leu(60) or Phe(77) are cleaved partially or not at all, respectively. (C) 1994 Academic Press, Inc.