Identification of the cellular receptor for anthrax toxin

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...

Full description

Saved in:
Bibliographic Details
Published in:Nature (London) 2001-11, Vol.414 (6860), p.225-229
Main Authors: Young, John A. T, Bradley, Kenneth A, Mogridge, Jeremy, Mourez, Michael, Collier, R. John
Format: Article
Language:English
Subjects:
Amino Acid Sequence
Animals
Anthrax
anthrax toxin
anthrax toxin receptor
anthrax toxin receptors
Antigens, Bacterial
Bacillus anthracis
Bacillus anthracis - chemistry
Bacteria
Bacterial Toxins - metabolism
Bacteriology
Biological and medical sciences
Cells
CHO Cells
Cloning
Cloning, Molecular
Cricetinae
edema factor
Fundamental and applied biological sciences. Psychology
Genetic Complementation Test
HeLa Cells
Humanities and Social Sciences
Humans
Immune system
lethal factor
letter
Mammals
Microbiology
Molecular Sequence Data
multidisciplinary
Pathogenicity, virulence, toxins, bacteriocins, pyrogens, host-bacteria relations, miscellaneous strains
protective antigen
Protein Binding
Protein Structure, Tertiary
Proteins
Receptors, Peptide - analysis
Receptors, Peptide - chemistry
Receptors, Peptide - genetics
Science
Science (multidisciplinary)
Sequence Alignment
Toxicity
Toxins
von Willebrand Factor - chemistry
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0028-0836
1476-4687
DOI:10.1038/n35101999