The cytoadherence ligand Plasmodium falciparum Erythrocyte Membrane Protein 1 (PfEMP1) binds to the P. falciparum Knob-associated Histidine-rich Protein (KAHRP) by electrostatic interactions

Plasmodium falciparum causes the most lethal form of human malaria claiming millions of lives each year world-wide. A distinctive feature of P. falciparum malaria is the adhesion of parasite-infected erythrocytes to the microvascular endothelium of various organs thereby avoiding clearance by the host immune system. Knob-like, electron-dense protrusions located at the surface of parasite-infected red blood cells act as attachment points between infected erythrocytes and endothelial cells. Cytoadherence is attributed to P. falciparum Erythrocyte Membrane Protein 1 (PfEMP1), a group of receptor proteins of about 200-350 kDa encoded by the parasite var genes. PfEMP1 is a family of antigenically variant, single-spanning membrane proteins localized to the knobs. The variable extracellular domain of PfEMP1 is responsible for cytoadherence and was shown to bind to a variety of endothelial receptors. The cytoplasmic domain of PfEMP1 (VAR sub(CD)) is remarkably well conserved and highly acidic. The predicted isoelectric point of VAR sub(CD) is 4.5.