Crystal Structure of the Anthrax Toxin Protective Antigen

Nature. 1997 Feb 27;385(6619):833-8. doi: 10.1038/385833a0.

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.

Publication types

  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Amino Acid Sequence
  • Antigens, Bacterial*
  • Bacillus anthracis / chemistry
  • Bacterial Toxins / chemistry*
  • Bacterial Toxins / toxicity
  • Binding Sites
  • Cell Membrane
  • Crystallography, X-Ray
  • Models, Biological
  • Models, Molecular
  • Molecular Sequence Data
  • Protein Conformation*

Substances

  • Antigens, Bacterial
  • Bacterial Toxins
  • anthrax toxin

Associated data

  • PDB/1ACC