Anthrax protective antigen (PA) (PA)

Anthrax protective antigen (PA) is an 83-kDa protein secreted by Bacillus anthracis that serves as the essential cell-binding component of the anthrax toxin. Its primary biological function is to mediate the delivery of the toxin's enzymatic components, lethal factor (LF) and edema factor (EF), into the host cell's cytosol (Source: UniProt P13423). PA binds to specific host cell surface receptors, such as capillary morphogenesis protein 2 (CMG2) and tumor endothelial marker 8 (TEM8), where it is proteolytically activated by furin-like proteases (Source: StatPearls). This activation allows PA to form a heptameric or octameric prepore, which then undergoes endocytosis and transforms into a membrane-spanning pore in the acidic environment of the endosome (Source: PubMed). Because PA is required for the entry of both LF and EF, it is the primary target for medical countermeasures against anthrax. Therapeutic monoclonal antibodies, such as raxibacumab and obiltoxaximab, work by binding to PA and preventing its interaction with host receptors, thereby neutralizing the toxin's effects (Source: FDA).

Other names

Protective antigenPA83pagAAnthrax toxin protective antigenProtective antigens

Therapeutic agents target the protective antigen (PA) to prevent its binding to host cell receptors, specifically capillary morphogenesis protein 2 (CMG2) and tumor endothelial marker 8 (TEM8). By neutralizing PA, these drugs inhibit the formation of the translocon pore, thereby blocking the entry of lethal factor (LF) and edema factor (EF) into the host cell cytosol (Source: FDA, StatPearls).