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Biochemical Characterization of the Interaction between the Extracellular Domain of a P. falciparum Invasion Ligand and Its Red Blood Cell Receptor♦

Biochemical Analysis of the Plasmodium falciparum Erythrocyte-binding Antigen-175 (EBA175)-Glycophorin-A Interaction. Implications for vaccine design
    Open AccessPublished:November 08, 2013DOI:https://doi.org/10.1074/jbc.P113.484840
        ♦ See referenced article, J. Biol. Chem. 2013, 288, 32106–32117
        The malaria parasite Plasmodium falciparum relies on a ligand called PfEBA175 to invade human red blood cells. Malaria researchers are spending much effort in targeting this protein for vaccine development. PfEBA175 binds to a protein receptor found on the surface of erythrocytes called glycophorin-A (GYPA). Previous studies of the PfEBA175-GYPA interaction have focused mostly on PfEBA175 subfragments known as Duffy-binding-like (DBL) domains because they can be expressed and are involved in GYPA binding. In this Paper of the Week, a team led by Gavin J. Wright at the Wellcome Trust Sanger Institute in the United Kingdom produced the whole extracellular domain of PfEBA175 in a mammalian expression system and analyzed its binding to GYPA on erythrocytes and in solution. By using various biochemical analyses, the investigators demonstrated that regions outside of the tandem DBL domains play a role in the interaction of PfEBA175 with GYPA. The authors say, “These data demonstrate the importance of PfEBA175 regions other than the DBL domains in the interaction with GYPA and merit their inclusion in an EBA175-based vaccine.”
        Figure thumbnail grfu1
        Full-length PfEBA175 binds GYPA and Neu5Acα2-3Gal with KD values of approximately 2.6 and 5.2 μm, respectively, whereas PfEBA175 region II binds both GYPA and Neu5Acα2-3Gal with a KD of approximately 25 μm.