Stephen H. Leppla

Anthrax toxin mechanisms of receptor binding and internalization

The anthrax toxin complex contains two catalytic proteins, edema factor (EF) and lethal factor (LF), which must be translocated to the cytosol of eukaryotic cells to cause toxicity. The third protein component of the toxin, protective antigen (PA), achieves this internalization. PA binds to cell surface receptors, is cleaved after the sequence Argl64-Lysl65-Lysl66-Argl67 by a cell surface protease, and thereby exposes a binding site to which EF or LF bind with high affinity. The complexes enter endosomes, which then become acidified, causing transfer of LF and EF to the cytosol.