title: [Molecular model of anthrax toxin translocation into target-cells].
abstract: Anthrax toxin is formed from three components: protective antigen (PA), lethal (LF) and edema (EF) factors. PA83 is cleaved by cell surface protease furin to produce a 63-kDa fragment (PA63). PA63 and LF/EF molecules are assembled to anthrax toxin complexes: oligomer PA63 x 7 + LF/EF x 3. Assembly is occurred during of binding with cellular receptor or near surface of target-cell. This toxin complex forms pore and induces receptor-mediated endocytosis. Formed endosome consists extracellular liquid with LF/EF and membrane-associated ferments (H+ and K+/Na+-ATPases) and proteins (receptors and others). H+ concentration is increased into endosome as result of K/Na-ATPase-dependent- activity of H+-ATPase. Difference of potentials (between endosome and intracellular liquid) is increased and LF/EF molecules are moved to pore and bound with PA63-oligomer to PA63 x 7 + LF/EF x 7 and full block pore (ion-selective channel). Endosome is increased in volume and induces increasing of PA63-oligomer pore to.size of effector complex: LF/EF x 7 + PAl7 x 7 = 750 kDa. Effector complex is translocated from endosome to cytosol by means high difference of potentials (H+) and dissociates from PA47 x 7 complex after cleavage of FFD315-sait by intracellular chymotrypsin-like proteases in all 7 molecules PA63. PA47 x 7 complex (strongly fixed in membrane with debris of hydrophobic loops) return into endosome and pore is destroyed. Endosome pH is decreased rapidly and PA47 x 7 complex is destroyed by endosomal/lysosomal proteases. Receptor-mediated endocytosis is ended by endosome recycling in cell-membrane.
authors.forename: A N
authors.initials: AN
authors.lastname: Noskov
mesh_terms: D000251:Adenosine Triphosphatases / Q000737:chemistry / Q000378:metabolism; D000881:Anthrax / Q000382:microbiology / Q000473:pathology*; D000942:Antigens, Bacterial / Q000737:chemistry / Q000633:toxicity*; D001408:Bacillus anthracis / Q000737:chemistry / Q000472:pathogenicity; D001427:Bacterial Toxins / Q000737:chemistry / Q000633:toxicity*; D004705:Endocytosis; D011992:Endosomes / Q000737:chemistry / Q000473:pathology; D006801:Humans; D008958:Models, Molecular
chemical_list: D000942:Antigens, Bacterial; D001427:Bacterial Toxins; C030325:anthrax toxin; D000251:Adenosine Triphosphatases