[Glycophorins of human erythrocytes as receptors for the malaria parasite Plasmodium falciparum]

Abstract

Malaria causes an estimated 300-500 million clinical cases in sub-Saharan Africa and Indochina. The most severe form of malaria is caused by Plasmodium falciparum, a parasite responsible for the death of 2 million children annually. Understanding the molecular basis of the parasite's invasion process is important for the development of new drugs and vaccines. Invasion of erythrocytes by the malaria parasite is a multistep process involving several specific interactions between the parasite's ligands and receptors on red blood cells. It was shown that glycophorins A, B, and C, sialoglycoproteins of human erythrocytes, act as receptors for Plasmodium falciparum ligands of the DBL family: EBA-175 and EBA-140 antigens. The binding specificity of EBA-175 is determined by the presence of sialic acid residues of the O-linked oligosaccharide chain clusters of glycphorin A and the amino-acid sequence, which contribute to their proper conformation. Glycophorin B, the next in terms of amount, can take on the role of glycophorin A as the receptor, but the glycophorin B- and sialic acid-dependent invasion of erythrocytes by Plasmodium falciparum involves a different parasite ligand. The third, and minor, glycophorin C appears to be the receptor for the antigen BAEBL, a paralogue of EBA-175. The binding of BAEBL to glycophorin C is dependent on the sialic acid residues of the O- and N-linked oligosaccharide chains and a peptide as well. It seems that the correct receptor site on glycophorin C needs to be elucidated in detail.