Assembled antigenic site

Although assembled antigenic sites are more numerous, both sites are topographic in that they are composed of structures on the protein surface. However, an antibody exerts high-affinity binding to segmental sites only when those sites are in a preferred conformation. Therefore, all determinants must be conformation specific. 

Anthrax toxin is composed of three proteins protective antigen (PA 83kDa), lethal factor (LF 90kDa), and edema factor (EF 89kDa). Individually, none of the three proteins are toxic but interact synergistically with at least one of the others. PA and LF (called LeTx) can cause lethal shock in experimental animals, and a mixture of PA and EF (edema toxin, EdTx) induces edema at the site of injection. Since two discrete units of the toxin are required for its action, the term binary toxin has been used to this and other bacterial toxins. Anthrax is unique from other binary toxins in that the binary moieties (EF and LF) interact only after being secreted from the bacteria. Further, EF and LF enter the cell via a single PA protein. Assembly of the three toxin proteins is initiated when PA binds to a proteinaceous cellular receptor and is activated by a member of the furin family of cellular proteases. The exact mechanisms of internalization of the toxin moieties are subject of scientific enquiry. Inside the cellular cytoplasm, EF (a calcium and calmodulin-dependent adenylate cyclase) causes a dramatic increase in intracellular cAMP concentrations and LF acts proteolytically to cleave certain MAPK kinases. 

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