1. McArdle Laboratory for Cancer Research, University of Wisconsin—Madison, 1400 University Avenue, Madison, Wisconsin 53706, USA
2. Biological and Biomedical Sciences Graduate Program, and
3. Department of Microbiology and Molecular Genetics, Harvard Medical School, 200 Longwood Avenue, Boston, Massachusetts 02115, USA
4. These authors contributed equally to the work
5. Present address: Department of Laboratory Medicine and Pathobiology, University of Toronto, 1 King's College Circle, Toronto, Ontario M5S 1A8, Canada.

Correspondence to: John A. T. Young¹ Correspondence and requests for materials should be addressed to J.A.T.Y. (e-mail: young@oncology.wisc.edu). The ATR cDNA clone has been deposited in GenBank (accession code AF421380).

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 phagocytosis^{1, 2}; lethal factor (LF) is a zinc-dependent protease that cleaves mitogen-activated protein kinase kinase and causes lysis of macrophages^{3, 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.