Bacillus anthracis protective antigen (PA)

Protective antigen (PA) is a critical 83-kDa protein component of the tripartite toxin secreted by Bacillus anthracis, the causative agent of anthrax [1]. PA serves as the essential cell-binding and translocation subunit for the two enzymatic components of the toxin: lethal factor (LF) and edema factor (EF) [2]. The process begins when PA binds to high-affinity host receptors, namely capillary morphogenesis gene 2 (CMG2) and tumor endothelial marker 8 (TEM8), where it is subsequently cleaved by host furin-like proteases into an active 63-kDa fragment [1][3]. This fragment oligomerizes into a prepore structure that captures LF and EF, undergoes endocytosis, and forms a membrane-spanning pore in the acidic environment of the endosome to deliver the toxins into the cytosol [2]. Because PA is required for the entry of both toxic factors, it is the primary target for anthrax vaccines and monoclonal antibody therapies [4][5]. Drugs such as raxibacumab and obiltoxaximab specifically target PA to neutralize its activity, effectively preventing the systemic toxemia associated with anthrax infection [4][5]. Sources: [1] UniProt Consortium. UniProtKB - P13423 (PAGA_BACAN). [2] Young JA, Collier RJ. Anthrax toxin: receptor binding, endocytosis, pore formation, and translocation. Annu Rev Biochem. 2007. [3] Friebe S, et al. The Ins and Outs of Anthrax Toxin Receptors. Cells. 2016. [4] FDA. Raxibacumab Prescribing Information. [5] FDA. Obiltoxaximab Prescribing Information.

Other names

Protective antigenPA83PA63pagA gene productAnthrax protective antigen

Monoclonal antibodies bind to the protective antigen (PA), preventing its interaction with host cell receptors (ANTXR1 and ANTXR2) or inhibiting the formation of the translocation pore, thereby neutralizing the entry of lethal factor (LF) and edema factor (EF) into the host cell cytoplasm [4][5].