Crystal structure of the anthrax toxin protective antigen View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

1997-02

AUTHORS

C Petosa, R J Collier, K R Klimpel, S H Leppla, R C Liddington

ABSTRACT

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. More... »

PAGES

833-838

Journal

TITLE

Nature

ISSUE

6619

VOLUME

385

Author Affiliations

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/385833a0

    DOI

    http://dx.doi.org/10.1038/385833a0

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1036639064

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/9039918


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