CD36 folding revealed by conformational epitope expression is essential for cytoadherence of Plasmodium falciparum-infected red blood cells

CD36 is a membrane glycoprotein and a putative scavenger receptor expressed by several cell types. In capillary endothelial cells, it mediates the adh erence of erythrocytes infected with Plasmodium falciparum. The CD36 sequen ce contains two hydrophobic domains located at the amino-and carboxyl-termi ni of the protein, but the topology of this protein and the functional sign ificance of these domains are still not clearly defined. We generated solub le CD36-IgG chimeric molecules by fusion of the extracellular domains of CD 36 with human immunoglobulin domains. The construct containing the N-terminal hydrophobic domain of CD36 was comp letely retained intracellularly as membrane-associated molecule, suggesting that the N-terminal hydrophobic domain of the CD36 is a real transmembrane domain and that CD36 has hairpin topology. A small amount of the CD36-IgG chimeric construct lacking both transmembrane domains escaped retention, wa s correctly processed, and accumulated in the extracellular medium as a sol uble molecule. This CD36-IgG construct failed to bind Plasmodium falciparum -infected erythrocytes. Using monoclonal antibodies specific for either con formational or structural epitopes, we demonstrate that failure of this CD3 6-IgG construct to bind infected erythrocytes was due to incorrect folding of the soluble chimeric molecule.