title: Serum protease cleavage of Bacillus anthracis protective antigen.
abstract: The protective antigen component of anthrax lethal toxin, produced in vitro, has a molecular mass of 83 kDa. Cell-culture studies by others have demonstrated that upon binding of the 83 kDa protective antigen to cell-surface receptors, the protein is cleaved by an unidentified cell-associated protease activity. The resultant 63 kDa protein then binds lethal factor to form lethal toxin, which has been proposed to be internalized by endocytosis. We found that, in the blood of infected animals, the protective antigen exists primarily as a 63 kDa protein and appears to be complexed with the lethal factor component of the toxin. Conversion of protective antigen from 83 to 63 kDa was catalysed by a calcium-dependent, heat-labile serum protease. Except for being complexed to protective antigen, there was no apparent alteration of lethal factor during the course of anthrax infection. The protective antigen-cleaving protease appeared to be ubiquitous among a wide range of animal species, including primates, horses, goats, sheep, dogs, cats and rodents.
authors.affiliation: Bacteriology Division, US Army Medical Research Institute of Infectious Diseases, Fort Detrick, Frederick, MD 21702-5011.
authors.forename: J W
authors.initials: JW
authors.lastname: Ezzell
authors.forename: T G
authors.initials: TG
authors.lastname: Abshire
mesh_terms: D000818:Animals; D000881:Anthrax / Q000378:metabolism*; D000911:Antibodies, Monoclonal; D000942:Antigens, Bacterial; D001408:Bacillus anthracis / Q000472:pathogenicity*; D001427:Bacterial Toxins / Q000378:metabolism*; D002118:Calcium / Q000494:pharmacology; D010450:Endopeptidases / Q000097:blood* / Q000187:drug effects / Q000494:pharmacology; D006168:Guinea Pigs; D010446:Peptide Fragments / Q000096:biosynthesis; D011480:Protease Inhibitors / Q000494:pharmacology; D051381:Rats
chemical_list: D000911:Antibodies, Monoclonal; D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D010446:Peptide Fragments; D011480:Protease Inhibitors; C030325:anthrax toxin; D010450:Endopeptidases; D002118:Calcium