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* Residue conservation analysis
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Gene Ontology (GO) functional annotation
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Cellular component
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extracellular region
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2 terms
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Biological process
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pathogenesis
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1 term
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Biochemical function
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protein binding
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2 terms
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DOI no:
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Nature
385:833-838
(1997)
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PubMed id:
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Crystal structure of the anthrax toxin protective antigen.
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C.Petosa,
R.J.Collier,
K.R.Klimpel,
S.H.Leppla,
R.C.Liddington.
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ABSTRACT
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Protective antigen (PA) is the central component of the three-part protein toxin
secreted by Bacillus anthracis, the organism responsible for anthrax. After
proteolytic activation on the host cell surface, PA forms a membrane-inserting
heptamer that translocates the toxic enzymes, oedema factor and lethal factor,
into the cytosol. PA, which has a relative molecular mass of 83,000 (M(r) 83K),
can also translocate heterologous proteins, and is being evaluated for use as a
general protein delivery system. Here we report the crystal structure of
monomeric PA at 2.1 A resolution and the water-soluble heptamer at 4.5 A
resolution. The monomer is organized mainly into antiparallel beta-sheets and
has four domains: an amino-terminal domain (domain 1) containing two calcium
ions and the cleavage site for activating proteases; a heptamerization domain
(domain 2) containing a large flexible loop implicated in membrane insertion; a
small domain of unknown function (domain 3); and a carboxy-terminal
receptor-binding domain (domain 4). Removal of a 20K amino-terminal fragment
from domain 1 allows the assembly of the heptamer, a ring-shaped structure with
a negatively charged lumen, and exposes a large hydrophobic surface for binding
the toxic enzymes. We propose a model of pH-dependent membrane insertion
involving the formation of a porin-like, membrane-spanning beta-barrel.
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Literature references that cite this PDB file's key reference
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PubMed id
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Reference
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K.L.Thoren,
and
B.A.Krantz
(2011).
The unfolding story of anthrax toxin translocation.
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Mol Microbiol, 80,
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Interactions of anthrax lethal factor with protective antigen defined by site-directed spin labeling.
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Proc Natl Acad Sci U S A, 108,
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| |
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|
| |
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|
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|
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|
| |
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PDB codes:
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G.K.Feld,
K.L.Thoren,
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|
| |
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PDB code:
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Proc Natl Acad Sci U S A, 107,
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PDB codes:
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R.A.Brady,
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The protective antigen component of anthrax toxin forms functional octameric complexes.
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PDB code:
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(2009).
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PDB code:
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PDB codes:
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and
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(2009).
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| |
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Toxicity of anthrax toxin is influenced by receptor expression.
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Multiple asparagine deamidation of Bacillus anthracis protective antigen causes charge isoforms whose complexity correlates with reduced biological activity.
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(2007).
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PDB code:
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Where a reference describes a PDB structure, the PDB
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