A molecular basis underlying differences in the toxicity of botulinum serotypes A and E

Mark Bajohrs, Colin Rickman, Thomas Binz, Bazbek Davletov

Research output: Contribution to journalArticlepeer-review

51 Citations (Scopus)


Botulinum neurotoxins (BoNTs) block neurotransmitter release through their specific proteolysis of the proteins responsible for vesicle exocytosis. Paradoxically, two serotypes of BoNTs, A and E, cleave the same molecule, synaptosome-associated protein with relative molecular mass 25K (SNAP-25), and yet they cause synaptic blockade with very different properties. Here we compared the action of BoNTs A and E on the plasma membrane fusion machinery composed of syntaxin and SNAP-25. We now show that the BoNT/A-cleaved SNAP-25 maintains its association with two syntaxin isoforms in vitro, which is mirrored by retention of SNAP-25 on the plasma membrane in vivo. In contrast, BoNT/E severely compromises the ability of SNAP-25 to bind the plasma membrane syntaxin isoforms, leading to dissociation of SNAP-25. The distinct properties of botulinum intoxication, therefore, can result from the ability of shortened SNAP-25 to maintain its association with syntaxins-in the case of BoNT/A poisoning resulting in unproductive syntaxin/SNAP-25 complexes that impede vesicle exocytosis.
Original languageEnglish
Pages (from-to)1090-5
Number of pages6
JournalEMBO Reports
Issue number11
Publication statusPublished - 2004


  • Animals
  • Antigens, Surface
  • Botulinum Toxins
  • Botulinum Toxins, Type A
  • Cell Membrane
  • Dose-Response Relationship, Drug
  • Glutathione Transferase
  • Immunoprecipitation
  • Membrane Proteins
  • Microscopy, Fluorescence
  • Models, Biological
  • Nerve Tissue Proteins
  • PC12 Cells
  • Plasmids
  • Protein Binding
  • Protein Isoforms
  • Qa-SNARE Proteins
  • Rats
  • Synapses
  • Synaptosomal-Associated Protein 25
  • Syntaxin 1


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