Protective antigen of anthrax toxin (PA)

Protective antigen (PA) is the essential 83 kDa cell-binding component of the tripartite anthrax toxin secreted by Bacillus anthracis [1.1.1, 1.3.1]. It functions as the delivery vehicle for the toxin's enzymatic subunits, lethal factor (LF) and edema factor (EF), which together cause the systemic symptoms and lethality of anthrax [1.1.2, 1.3.2]. PA binds to host cell receptors, primarily tumor endothelial marker 8 (TEM8) and capillary morphogenesis gene 2 (CMG2), where it is cleaved by host furin-like proteases into a 63 kDa active form (PA63) [1.2.1, 1.4.1]. This activated PA oligomerizes into a heptameric or octameric prepore that captures LF and EF, facilitating their endocytosis and subsequent translocation into the cytosol through a pH-dependent membrane pore [1.2.2, 1.3.3]. Because PA is required for the entry of both toxic enzymes, it is the primary target for therapeutic antibodies like raxibacumab and obiltoxaximab, which neutralize the toxin by blocking PA's interaction with host receptors [1.4.2, 1.5.1]. PA is also the principal immunogen in licensed anthrax vaccines, eliciting protective antibodies that prevent infection [1.2.1, 1.5.3].

Other names

Anthrax protective antigenPA83PA63pagA proteinAnthrax toxin protective antigen

Neutralization of the protective antigen (PA) to prevent its binding to host cell receptors (ANTXR1 and ANTXR2), thereby inhibiting the formation of the toxin pore and the subsequent translocation of lethal factor (LF) and edema factor (EF) into the host cell cytosol [1.3.3, 1.4.2].