title: Identification of the cellular receptor for anthrax toxin.
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 phagocytosis; lethal factor (LF) is a zinc-dependent protease that cleaves mitogen-activated protein kinase kinase and causes lysis of macrophages. 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.
authors.affiliation: McArdle Laboratory for Cancer Research, University of Wisconsin-Madison, 1400 University Avenue, Madison, Wisconsin 53706, USA.
authors.forename: K A
authors.initials: KA
authors.lastname: Bradley
authors.forename: J
authors.initials: J
authors.lastname: Mogridge
authors.forename: M
authors.initials: M
authors.lastname: Mourez
authors.forename: R J
authors.initials: RJ
authors.lastname: Collier
authors.forename: J A
authors.initials: JA
authors.lastname: Young
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000942:Antigens, Bacterial; D001408:Bacillus anthracis / Q000737:chemistry*; D001427:Bacterial Toxins / Q000378:metabolism*; D016466:CHO Cells; D003001:Cloning, Molecular; D006224:Cricetinae; D005816:Genetic Complementation Test; D006367:HeLa Cells; D006801:Humans; D008969:Molecular Sequence Data; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D018000:Receptors, Peptide / Q000032:analysis* / Q000737:chemistry / Q000235:genetics; D016415:Sequence Alignment; D014841:von Willebrand Factor / Q000737:chemistry
chemical_list: D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D018000:Receptors, Peptide; C030325:anthrax toxin; C070309:anthrax toxin receptors; D014841:von Willebrand Factor