How anthrax toxins cause pathology. Fully virulent B. anthracis produce an antiphagocytic capsule as well as toxins. The protective antigen (PA) of the anthrax toxin binds to the ATR on the host cell surface. The 83-kDa form of PA is cleaved by the cell surface protease furin and produces a 63-kDa monomer. Heptamerization of PA induces clustering of the ATRs, association of the complex with lipid rafts, and exposure of binding domains to the edema factor (EF) or the lethal factor (LF). The heptamer, and bound EF or LF, are then endocytosed. EF, an adenylate cyclase, and LF, a Zn²⁺ metalloprotease, translocate to the cytosol through a pore created in the membrane and act on host cytosolic targets to induce edema, necrosis, and hypoxia. Modified with permission from Annual Reviews (4). CaM, calmodulin.