Botulinum Neurotoxin Type G Proteolyses the Ala⁸¹-Ala⁸² Bond of Rat Synaptobrevin 2

Abstract

Tetanus toxin and the botulinum neurotoxins types A to F inhibit neurotransmitter release from presynaptic nerve endings by selectively proteolysing the synaptic proteins synaptobrevin, syntaxin, or SNAP-25. Here, we show that botulinum toxin type G cleaves rat synaptobrevin 2 between Ala⁸¹ and Ala⁸², a peptide bond that differs from those attacked by tetanus toxin and the botulinal toxins types B, D, and F. Synaptobrevin isoforms carrying a Gly in the P1 position are poor substrates. Analyses of N-terminal deletion mutants of rat synaptobrevin 2 showed that a substrate starting at Leu⁵⁴ is cleaved efficiently, whereas substrates beginning at Leu⁶⁰ or Phe⁷⁷ are cleaved partially or not at all, respectively.