Anthrax toxin protective antigen (PA)

Anthrax toxin protective antigen (PA) is a critical 83-kDa protein component of the tripartite toxin secreted by Bacillus anthracis, the causative agent of anthrax [UniProt]. PA functions as the essential delivery mechanism for the toxin's enzymatic subunits, lethal factor (LF) and edema factor (EF). Upon secretion, PA binds to high-affinity host cell receptors, such as capillary morphogenesis gene 2 (CMG2) or tumor endothelial marker 8 (TEM8), where it is cleaved by furin-like proteases into a 63-kDa active form (PA63) [PubMed]. This active form oligomerizes into a heptameric or octameric prepore that captures LF and EF, facilitating their endocytosis and subsequent translocation into the cytosol via a pH-dependent pore [UniProt, PubMed]. Because PA is the common mediator for both lethal and edema toxin entry, it is the primary target for medical countermeasures, including the anthrax vaccine and neutralizing monoclonal antibodies like raxibacumab and obiltoxaximab [FDA, CDC].

Other names

PA83PA63pagAProtective antigen proteinAnthrax toxin PA

Neutralizing monoclonal antibodies bind to the PA83 or PA63 subunits of the protective antigen, sterically hindering the interaction between the toxin and host receptors (CMG2/TEM8) or preventing the formation of the heptameric pore, thereby blocking the entry of lethal factor (LF) and edema factor (EF) into the host cell [FDA, PubMed].