Structure and activity of a functional derivative of Clostridium botulinum neurotoxin B

Geoffrey Masuyer, M Beard, V A Cadd, J A Chaddock, K Ravi Acharya

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Botulinum neurotoxins (BoNTs) cause flaccid paralysis by inhibiting neurotransmission at cholinergic nerve terminals. BoNTs consist of three essential domains for toxicity: the cell binding domain (Hc), the translocation domain (Hn) and the catalytic domain (LC). A functional derivative (LHn) of the parent neurotoxin B composed of Hn and LC domains was recombinantly produced and characterised. LHn/B crystallographic structure at 2.8 angstrom resolution is reported. The catalytic activity of LHn/B towards recombinant human VAMP was analysed by substrate cleavage assay and showed a higher specificity for VAMP-1,-2 compared to VAMP-3. LHn/B also showed measurable activity in living spinal cord neurons. Despite lacking the Hc (cell-targeting) domain, LHn/B retained the capacity to internalize and cleave intracellular VAMP-1 and -2 when added to the cells at high concentration. These activities of the LHn/B fragment demonstrate the utility of engineered botulinum neurotoxin fragments as analytical tools to study the mechanisms of action of BoNT neurotoxins and of SNARE proteins.
Original languageEnglish
Pages (from-to)52-57
Number of pages6
JournalJournal of Structural Biology
Issue number1
Publication statusPublished - Apr 2011


  • protein engineering
  • botulinum neurotoxin
  • crystal structure


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