Protective antigen (PA) (PA)

Protective antigen (PA) is a critical 83-kDa protein component of the tripartite toxin produced by Bacillus anthracis, the causative agent of anthrax [UniProt: P04133]. PA serves as the essential delivery vehicle for the toxin's enzymatic components, lethal factor (LF) and edema factor (EF) [PubMed: 12776166]. Upon secretion, PA binds to high-affinity host cell receptors, specifically tumor endothelial marker 8 (TEM8) and capillary morphogenesis protein 2 (CMG2) [PubMed: 11546870]. Following binding, PA is cleaved by host furin-like proteases into a 63-kDa fragment (PA63), which oligomerizes into a heptameric or octameric prepore [PubMed: 15343330]. This structure then captures LF and EF, facilitating their endocytosis and subsequent translocation into the cytosol through a pH-dependent pore [PubMed: 12776166]. Because PA is essential for the entry of both lethal and edema toxins into cells, it is the primary target for anthrax vaccines and therapeutic monoclonal antibodies like raxibacumab and obiltoxaximab [FDA: Raxibacumab Label]. These drugs work by neutralizing PA, thereby preventing the assembly of the active toxin complex and protecting the host from the devastating effects of the infection [PubMed: 19605824].

Other names

PA83PA63pagAAnthrax protective antigenProtective antigen protein

Neutralization of the PA component to prevent binding to host receptors (ANTXR1/ANTXR2), inhibition of PA oligomerization, and prevention of the translocation of lethal factor and edema factor into the host cell cytosol [FDA: Raxibacumab Label, PubMed: 19605824].