Sep. 10, 2021
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Bacillus anthracis produces the three subunits of anthrax toxin: protective antigen (PA), lethal factor (LF) and edema factor (EF). The 83 kDa form of PA (PA83) binds to either of two type I transmembrane proteins (CMG2 or TEM8) at the cell surface, where it is cleaved by furin-like proteases, leading to the shorter receptor-associated form of PA (PA63) and a soluble fragment (PA20). Upon toxin binding, the receptors are phosphorylated by Srcâlike kinases (Src or Fyn), and are ubiquitinated (by Cbl for TEM8, or by an unknown E3 ligase for CMG2). After oligomerization in lipid rafts (dark grey), the receptor-toxin complex is internalized by endocytosis, a process involving clathrin, dynamin, activator protein 1 (APâ1), actin, and low-density lipoprotein receptor-related protein 6 (LRP6). (Source: Friebe S, van der Goot FG, Bürgi J. The ins and outs of anthrax toxin. Toxins (Basel) 2016;8(3). Creative Commons by Attribution (CC-BY) License.)