Abstract
The tripartite toxin secreted by Bacillus anthracis, the causative agent of anthrax, helps the bacterium evade the immune system and can kill the host during a systemic infection. Two components of the toxin enzymatically modify substrates within the cytosol of mammalian cells: oedema factor (OF) is an adenylate cyclase that impairs host defences through a variety of mechanisms including inhibiting phagocytosis1,2; lethal factor (LF) is a zinc-dependent protease that cleaves mitogen-activated protein kinase kinase and causes lysis of macrophages3,4,5. Protective antigen (PA), the third component, binds to a cellular receptor and mediates delivery of the enzymatic components to the cytosol. Here we describe the cloning of the human PA receptor using a genetic complementation approach. The receptor, termed ATR (anthrax toxin receptor), is a type I membrane protein with an extracellular von Willebrand factor A domain that binds directly to PA. In addition, a soluble version of this domain can protect cells from the action of the toxin.
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Acknowledgements
We thank K. Schell and members of the flow cytometry facility at the University of Wisconsin Comprehensive Cancer Center for performing the cell sorting. This work was supported by a grant to J.A.T.Y. and R.J.C. from the National Institutes of Health. J.M. was supported in part by a Medical Research Council (Canada) postdoctoral fellowship.
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R.J.C. holds financial interest in AVANT Immunotherapeutics and PharmAthene, Inc.
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Bradley, K., Mogridge, J., Mourez, M. et al. Identification of the cellular receptor for anthrax toxin. Nature 414, 225–229 (2001). https://doi.org/10.1038/n35101999
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DOI: https://doi.org/10.1038/n35101999
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