Role of human protein disulfide isomerase (PDI) in the redox regulation of anthrax receptor 2 (ANTXR2)
Anthrax is an acute infectious disease caused by B. anthracis, a gram-positive and spore-forming bacterium. Anthrax toxin is a tripartite AB toxin composed of a receptor binding/pore-forming moiety, protective antigen (PA), and two catalytic moieties, edema factor (EF) and lethal factor (LF). Anthrax toxin PA binds to cell-surface receptors, where it gets activated by furin, and assembles into a ring-like heptameric structure. The toxin-receptor complex is internalized into endosomes where the acidic pH triggers PA pore formation on the endosomal membrane that translocates the toxin catalytic moieties. Recent study has shown that anthrax toxin receptors play a critical role in anthrax toxin action. Reduction of the disulfides of the R2-Ig domain significantly inhibited the release of K+ through the PA pore formed on the liposomal membranes and the release of K + through the plasma membranes of the CHO cells over-expressing ANTRXR2. Disruption of the disulfides in R2-Ig also inhibited the PA-mediated LF N translocation across the plasma membrane, suggesting that anthrax toxin cellular internalization and trafficking may be influenced by cellular redox regulators. In this study, we investigated the role of PDI in the refolding of ANTXR2 in vitro. Purified PDI was shown to partially summarize the mis-matched disulfide bonds in the recombinant extracellular domain of ANTXR2, demonstrating that PDI may be involved in the redox regulation of the receptor disulfide bonds in vivo.
Alshrif, Naima Mohamed, "Role of human protein disulfide isomerase (PDI) in the redox regulation of anthrax receptor 2 (ANTXR2)" (2012). ETD Collection for University of Texas, El Paso. AAI1533203.