THE PLASMODIUM-FALCIPARUM CD36 INTERACTION IS MODIFIED BY A SINGLE AMINO-ACID SUBSTITUTION IN CD36

CD36 is an 88-kD glycoprotein involved in the cytoadherence of Plasmod ium falciparum-parasitized erythrocytes (PE) to endothelial cells. The molecular mechanisms involved in CD36-dependent cytoadherence were ex amined by expressing three CD36 homologues (human, murine, and rat) in COS-7 cells and observing their PE-binding characteristics over a pH range of 6.0 to 7.4 and following iodination of these receptors. PE bi nding to human CD36 was pH dependent, with peak binding at pH 6.8 to 7 .0, and binding was unaffected by iodination. In contrast, PE adherenc e to murine and rat CD36 was insensitive to changes in pH, and iodinat ion significantly reduced binding. We further show that the difference s observed in the binding phenotype of human and rodent CD36 can be at tributed to a single residue, Site-directed mutagenesis of the histidi ne at position 242 of human CD36 to tyrosine (found in rodent CD36) co nferred the binding phenotype of rodent CD36 onto human CD36. Furtherm ore, substitution of the tyrosine at position 242 of rat CD36 for hist idine conferred the binding phenotype of human CD36 onto rat CD36. The se findings suggest that residue 242 is part of, or important to the c onformation of, the PE-binding domain of CD36. (C) 1998 by The America n Society of Hematology.