Botulinum neurotoxins serotypes A and E cleave SNAP‐25 at distinct COOH‐terminal peptide bonds

Giampietro Schiavo(University of Padua), Annalisa Santucci(University of Siena), Bibhuti R. DasGupta, Prashant Mehta(Scripps Research Institute), Jaime Jontes(Scripps Research Institute), Fabio Benfenati(University of Rome Tor Vergata), Michael C. Wilson(Scripps Research Institute), Cesare Montecucco(University of Padua)
FEBS Letters
November 29, 1993
10.1016/0014-5793(93)80448-4
Cited by 441

Abstract

SNAP-25, a membrane-associated protein of the nerve terminal, is specifically cleaved by botulinum neurotoxins serotypes A and E, which cause human and animal botulism by blocking neurotransmitter release at the neuromuscular junction. Here we show that these two metallo-endopeptidase toxins cleave SNAP-25 at two distinct carboxyl-terminal sites. Serotype A catalyses the hydrolysis of the Gln197-Arg198 peptide bond, while serotype E cleaves the Arg180-Ile181 peptide lineage. These results indicate that the carboxyl-terminal region of SNAP-25 plays a crucial role in the multi-protein complex that mediates vesicle docking and fusion at the nerve terminal.

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