BOTULINUM NEUROTOXIN TYPE-C CLEAVES A SINGLE LYS-ALA BOND WITHIN THE CARBOXYL-TERMINAL REGION OF SYNTAXINS

Botulinum neurotoxin serotype C (BoNT/C) is a 150-kDa protein produced by Clostridium botulinum, which causes animal botulism. In contrast t o the other botulinum neurotoxins that contain one atom of zinc, highl y purified preparations of BoNT/C bind two atoms of zinc per toxin mol ecule. BoNT/C is a zinc endopeptidase that cleaves syntaxin 1A at the Lys(253)-Ala(254) and syntaxin 1B at the Lys(252)-Ala(253) peptide bon ds, only when they are inserted into a lipid bilayer. The other Lys-Al a bond present within the carboxyl-terminal region is not hydrolyzed. Syntaxin isoforms 2 and 3 are also cleaved by BoNT/C, while syntaxin 4 is resistant. These data suggest that BoNT/C recognizes a specific sp atial organization of syntaxin, adopted upon membrane insertion, which brings a selected Lys-Ala peptide bond of its carboxyl-terminal regio n to the active site of this novel metalloproteinase.