1ACC

ANTHRAX PROTECTIVE ANTIGEN

Summary for 1ACC

• Entry DOI: 10.2210/pdb1acc/pdb
• Descriptor: ANTHRAX PROTECTIVE ANTIGEN, CALCIUM ION (3 entities in total)
• Functional Keywords: toxin, calcium-binding
• Biological source: Bacillus anthracis
• Cellular location: Secreted, extracellular space: P13423
• Total number of polymer chains: 1
• Total formula weight: 82849.97

Authors

Petosa, C.,Liddington, R.C. (deposition date: 1997-02-05, release date: 1998-02-11, Last modification date: 2024-02-07)

Primary citation

Petosa, C.,Collier, R.J.,Klimpel, K.R.,Leppla, S.H.,Liddington, R.C.
Crystal structure of the anthrax toxin protective antigen.
Nature, 385:833-838, 1997

PubMed 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.

PubMed: 9039918
DOI: 10.1038/385833a0

Experimental method

X-RAY DIFFRACTION (2.1 Å)