Changing the Receptor Specificity of Anthrax Toxin

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Changing the Receptor Specificity of Anthrax Toxin

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Title: Changing the Receptor Specificity of Anthrax Toxin
Author: Mechaly, Adva; McCluskey, Andrew Jeffrey; Collier, R. J

Note: Order does not necessarily reflect citation order of authors.

Citation: Mechaly, Adva, Andrew J. McCluskey, and R. John Collier. 2012. Changing the receptor specificity of anthrax toxin. mBio 3(3): e00088-12.
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Abstract: The actions of many bacterial toxins depend on their ability to bind to one or more cell-surface receptors. Anthrax toxin acts by a sequence of events that begins when the protective-antigen (PA) moiety of the toxin binds to either one of two cell-surface proteins, ANTXR1 and ANTXR2, and is proteolytically activated. The activated PA self-associates to form oligomeric pore precursors, which, in turn, bind the enzymatic moieties of the toxin and transport them to the cytosol. We introduced a double mutation into domain 4 of PA to ablate its native receptor-binding function and fused epidermal growth factor (EGF) to the C terminus of the mutated protein. The resulting fusion protein transported enzymatic effector proteins into a cell line that expressed the EGF receptor (A431 cells), but not into a line lacking this receptor (CHO-K1 cells). Addition of excess free EGF blocked transport of effector proteins into A431 cells via the fusion protein, but not via native PA. We also showed that fusing the diphtheria toxin receptor-binding domain to the C terminus of the mutated PA channeled effector-protein transport through the diphtheria toxin receptor. PA fusion proteins with altered receptor specificity may be useful in biological research and could have practical applications, including ablation or perturbation of selected populations of cells in vivo.
Published Version: doi:10.1128/mBio.00088-12
Other Sources: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3569862/pdf/
Terms of Use: This article is made available under the terms and conditions applicable to Other Posted Material, as set forth at http://nrs.harvard.edu/urn-3:HUL.InstRepos:dash.current.terms-of-use#LAA
Citable link to this page: http://nrs.harvard.edu/urn-3:HUL.InstRepos:11181135
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