Identification of the cellular receptor for anthrax toxin

Nature. 2001 Nov 8;414(6860):225-9. doi: 10.1038/n35101999.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Antigens, Bacterial*
  • Bacillus anthracis / chemistry*
  • Bacterial Toxins / metabolism*
  • CHO Cells
  • Cloning, Molecular
  • Cricetinae
  • Genetic Complementation Test
  • HeLa Cells
  • Humans
  • Molecular Sequence Data
  • Protein Binding
  • Protein Structure, Tertiary
  • Receptors, Peptide / analysis*
  • Receptors, Peptide / chemistry
  • Receptors, Peptide / genetics
  • Sequence Alignment
  • von Willebrand Factor / chemistry


  • Antigens, Bacterial
  • Bacterial Toxins
  • Receptors, Peptide
  • anthrax toxin
  • anthrax toxin receptors
  • von Willebrand Factor

Associated data

  • GENBANK/AF421380