Structure and function of anthrax toxin.
Anthrax toxin is a binary A-B toxin comprised of protective antigen (PA) and two enzymatic moieties, edema factor (EF) and lethal factor (LF). In the presence of a host cell-surface receptor, PA can mediate the delivery of EF and LF from the extracellular milieu into the host cell cytosol to effect toxicity. In this delivery, PA undergoes multiple structural changes--from a monomer to a heptameric prepore to a membrane-spanning heptameric pore. The catalytic factors also undergo dramatic structural changes as they unfold to allow for their translocation across the endosomal membrane and refold to preserve their catalytic activity within the cytosol. In addition to these gross structural changes, the intoxication mechanism depends on the ability of PA to form specific interactions with the host cell receptor, EF, and LF. This chapter presents a review of experiments probing these structural interactions and rearrangements in the hopes of gaining a molecular understanding of toxin action.
Lacy
D B
DB
Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, MA 02115, USA.
Collier
R J
RJ
D000818:Animals; D000942:Antigens, Bacterial; D001408:Bacillus anthracis / Q000737:chemistry* / Q000472:pathogenicity; D001427:Bacterial Toxins / Q000737:chemistry* / Q000378:metabolism*; D001665:Binding Sites; D001692:Biological Transport; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D004705:Endocytosis; D006801:Humans; D008958:Models, Molecular; D017434:Protein Structure, Tertiary; D011956:Receptors, Cell Surface / Q000378:metabolism
D000942:Antigens, Bacterial; D001427:Bacterial Toxins; D002352:Carrier Proteins; D011956:Receptors, Cell Surface; C030325:anthrax toxin