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.
MeSH terms
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Amino Acid Sequence
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Animals
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Base Sequence
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Binding Sites / genetics
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Botulinum Toxins / chemistry
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Botulinum Toxins / genetics
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Botulinum Toxins / toxicity*
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DNA Primers / genetics
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Endopeptidases / chemistry
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Endopeptidases / genetics
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Endopeptidases / toxicity
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In Vitro Techniques
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Membrane Proteins / genetics
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Membrane Proteins / metabolism*
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Molecular Sequence Data
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Nerve Tissue Proteins / genetics
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Nerve Tissue Proteins / metabolism*
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Neurotransmitter Agents / metabolism
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Protein Conformation
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R-SNARE Proteins
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Rats
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Sequence Deletion
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Substrate Specificity
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Synaptic Vesicles / drug effects
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Synaptic Vesicles / physiology
Substances
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DNA Primers
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Membrane Proteins
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Nerve Tissue Proteins
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Neurotransmitter Agents
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R-SNARE Proteins
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Endopeptidases
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Botulinum Toxins