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


Reference:

Masuyer, G., Beard, M., Cadd, V. A., Chaddock, J. A. and Acharya, K. R., 2011. Structure and activity of a functional derivative of Clostridium botulinum neurotoxin B. Journal of Structural Biology, 174 (1), pp. 52-57.

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    Official URL:

    http://dx.doi.org/10.1016/j.jsb.2010.11.010

    Abstract

    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.

    Details

    Item Type Articles
    CreatorsMasuyer, G., Beard, M., Cadd, V. A., Chaddock, J. A. and Acharya, K. R.
    DOI10.1016/j.jsb.2010.11.010
    Uncontrolled Keywordsprotein engineering, botulinum neurotoxin, crystal structure, snare
    DepartmentsFaculty of Science > Biology & Biochemistry
    RefereedYes
    StatusPublished
    ID Code23520

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