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STRUCTURE OF A FUNCTIONAL DERIVATIVE OF CLOSTRIDIUM BOTULINUM NEUROTOXIN TYPE BSTRUCTURE OF A FUNCTIONAL DERIVATIVE OF CLOSTRIDIUM BOTULINUM NEUROTOXIN TYPE B
Structural highlights
Publication Abstract from PubMedBotulinum 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 2.8A 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. Structure and activity of a functional derivative of Clostridium botulinum neurotoxin B.,Masuyer G, Beard M, Cadd VA, Chaddock JA, Acharya KR J Struct Biol. 2010 Nov 13. PMID:21078393[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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