|dc.description.abstract||Plasmodium falciparum is the parasite responsible for causing most cases of malaria. While the pathogenesis of the disease is variable, severe malaria is often associated with the sequestration of parasite infected erythrocytes (IE s) in various organs of the body. The sequestration of IE s is due to adhesion molecules called Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) on the surface of IE s. PfEMP1 adheres to various host receptors on the surfaces of the endothelial cells in various tissues. ICAM-1 is the receptor in the brain that is believed to be responsible for the sequestering of IE s which is associated with the disease cerebral malaria.
In this paper, threonine (aa837), glutamate (aa834), and lysine (aa831) of the DBL2βC2 region of the PfEMP1 A4tres, were converted to alanine using site specific mutagenesis. These residues were chosen using a comparative modeling program that formed a plausible 3D structure of the DBL2βC2 region. Binding / Immunofluorescence assays were performed to characterize ICAM-1 binding in each mutant. The results of these assays showed that lysine was probably not involved in binding ICAM-1 while threonine may be involved in ICAM-1 binding. Also, changing glutamate to alanine increased binding suggesting that it is of structural significance.||en_US