NCJ Number
192805
Journal
Nature Volume: 414 Dated: November 8, 2001 Pages: 225-229
Date Published
November 2001
Length
5 pages
Annotation
This paper discusses 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 defenses 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. This paper describes 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. The study used six methods, including mutagenesis and characterization of CHO-K1 cells, cDNA complementation, and GST-D4 pull-down assay. Figures, notes