title: The lethal and edema factors of anthrax toxin bind only to oligomeric forms of the protective antigen.
abstract: The three proteins that comprise anthrax toxin, edema factor (EF), lethal factor (LF), and protective antigen (PA), assemble at the mammalian cell surface into toxic complexes. After binding to its receptor, PA is proteolytically activated, yielding a carboxyl-terminal 63-kDa fragment (PA(63)) that coordinates assembly of the complexes, promotes their endocytosis, and translocates EF and LF to the cytosol. PA(63) spontaneously oligomerizes to form symmetric ring-shaped heptamers that are capable of binding three molecules of EF and/or LF as competing ligands. To determine whether binding of these ligands depends on oligomerization of PA(63), we prepared two oligomerization-deficient forms of this protein, each mutated on a different PA(63)-PA(63) contact face. In solution or when bound to receptors on Chinese hamster ovary K1 cells, neither mutant alone bound ligand, but a mixture of them did. After the two mutants were proteolytically activated and mixed with ligand in solution, a ternary complex was isolated containing one molecule of each protein. Thus EF and LF bind stably only to PA(63) dimers or higher order oligomers. These findings are relevant to the kinetics and pathways of assembly of anthrax toxin complexes.
authors: Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, MA 02115, USA.
authors: Jeremy
authors: J
authors: Mogridge
authors: Kristina
authors: K
authors: Cunningham
authors: D Borden
authors: DB
authors: Lacy
authors: Michael
authors: M
authors: Mourez
authors: R John
authors: RJ
authors: Collier
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism*; D000942:Antigens, Bacterial / Q000235:genetics / Q000378:metabolism*; D001408:Bacillus anthracis / Q000378:metabolism*; D001427:Bacterial Toxins / Q000235:genetics / Q000378:metabolism*; D008024:Ligands; D016296:Mutagenesis; D009842:Oligopeptides / Q000378:metabolism; D012996:Solutions
chemical_list: D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D008024:Ligands; D009842:Oligopeptides; D012996:Solutions; C030325:anthrax toxin; D000262:Adenylyl Cyclases