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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, Non-P.H.S.
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Animals
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Binding Sites
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Botulinum Toxins / metabolism*
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Brain Chemistry
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Hydrolysis
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Immunoblotting
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Membrane Proteins*
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Molecular Sequence Data
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Nerve Tissue Proteins / chemistry
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Nerve Tissue Proteins / metabolism*
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Peptide Fragments / chemistry
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Peptide Fragments / isolation & purification
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Peptide Fragments / metabolism
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Rats
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Recombinant Proteins / metabolism
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Synaptosomal-Associated Protein 25
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Synaptosomes / chemistry
Substances
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Membrane Proteins
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Nerve Tissue Proteins
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Peptide Fragments
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Recombinant Proteins
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Snap25 protein, rat
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Synaptosomal-Associated Protein 25
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Botulinum Toxins