Details

Autor(en) / Beteiligte

• Young, John A. T
• Bradley, Kenneth A
• Mogridge, Jeremy
• Mourez, Michael
• Collier, R. John

Titel

Identification of the cellular receptor for anthrax toxin

Ist Teil von

• Nature (London), 2001-11, Vol.414 (6860), p.225-229

Ort / Verlag

London: Nature Publishing

Erscheinungsjahr

2001

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.