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 Plasmodium falciparum-parasitized erythrocytes (PE) to endothelial cells. The molecular mechanisms involved in CD36-dependent cytoadherence were examined 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 binding 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 adherence to murine and rat CD36 was insensitive to changes in pH, and iodination significantly reduced binding. We further show that the differences observed in the binding phenotype of human and rodent CD36 can be attributed to a single residue. Site-directed mutagenesis of the histidine at position 242 of human CD36 to tyrosine (found in rodent CD36) conferred the binding phenotype of rodent CD36 onto human CD36. Furthermore, substitution of the tyrosine at position 242 of rat CD36 for histidine conferred the binding phenotype of human CD36 onto rat CD36. These findings suggest that residue 242 is part of, or important to the conformation of, the PE-binding domain of CD36.
Institute of Medical Science, Department of Medicine, University of Toronto; and the Tropical Disease Unit, The Toronto Hospital, Toronto, Canada.
L
L
Serghides
I
I
Crandall
E
E
Hull
K C
KC
Kain
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D018955:CD36 Antigens / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D019556:COS Cells; D002448:Cell Adhesion; D004912:Erythrocytes / Q000469:parasitology / Q000502:physiology; D005434:Flow Cytometry; D006639:Histidine / Q000235:genetics; D006801:Humans; D006863:Hydrogen-Ion Concentration; D051379:Mice; D008969:Molecular Sequence Data; D007470:Monoiodotyrosine / Q000737:chemistry; D016297:Mutagenesis, Site-Directed; D010963:Plasmodium falciparum / Q000378:metabolism*; D051381:Rats; D013329:Structure-Activity Relationship; D014443:Tyrosine / Q000737:chemistry / Q000235:genetics
D018955:CD36 Antigens; D014443:Tyrosine; D006639:Histidine; D007470:Monoiodotyrosine