title: Botulinum neurotoxins serotypes A and E cleave SNAP-25 at distinct COOH-terminal peptide bonds.
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.
authors.affiliation: Centro CNR Biomembrane, Università di Padova, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Schiavo
authors.forename: A
authors.initials: A
authors.lastname: Santucci
authors.forename: B R
authors.initials: BR
authors.lastname: Dasgupta
authors.forename: P P
authors.initials: PP
authors.lastname: Mehta
authors.forename: J
authors.initials: J
authors.lastname: Jontes
authors.forename: F
authors.initials: F
authors.lastname: Benfenati
authors.forename: M C
authors.initials: MC
authors.lastname: Wilson
authors.forename: C
authors.initials: C
authors.lastname: Montecucco
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D001905:Botulinum Toxins / Q000378:metabolism*; D001923:Brain Chemistry; D006868:Hydrolysis; D015151:Immunoblotting; D008565:Membrane Proteins; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000378:metabolism*; D010446:Peptide Fragments / Q000737:chemistry / Q000302:isolation & purification / Q000378:metabolism; D051381:Rats; D011994:Recombinant Proteins / Q000378:metabolism; D050825:Synaptosomal-Associated Protein 25; D013574:Synaptosomes / Q000737:chemistry
chemical_list: D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D010446:Peptide Fragments; D011994:Recombinant Proteins; C494210:Snap25 protein, rat; D050825:Synaptosomal-Associated Protein 25; D001905:Botulinum Toxins