Sequence similarity between the erythrocyte binding domain 1 of the Plasmodium vivax Duffy binding protein and the V3 loop of HIV-1 strain MN reveals binding residues for the Duffy Antigen Receptor for Chemokines

Abstract

<p>Abstract</p> <p>Background</p> <p>The surface glycoprotein (SU, gp120) of the human immunodeficiency virus (HIV) must bind to a chemokine receptor, CCR5 or CXCR4, to invade CD4+ cells. <it>Plasmodium vivax </it>uses the Duffy Binding Protein (DBP) to bind the Duffy Antigen Receptor for Chemokines (DARC) and invade reticulocytes.</p> <p>Results</p> <p>Variable loop 3 (V3) of HIV-1 SU and domain 1 of the <it>Plasmodium vivax </it>DBP share a sequence similarity. The site of amino acid sequence similarity was necessary, but not sufficient, for DARC binding and contained a consensus heparin binding site essential for DARC binding. Both HIV-1 and <it>P. vivax </it>can be blocked from binding to their chemokine receptors by the chemokine, RANTES and its analog AOP-RANTES. Site directed mutagenesis of the heparin binding motif in members of the DBP family, the <it>P. knowlesi </it>alpha, beta and gamma proteins abrogated their binding to erythrocytes. Positively charged residues within domain 1 are required for binding of <it>P. vivax </it>and <it>P. knowlesi </it>erythrocyte binding proteins.</p> <p>Conclusion</p> <p>A heparin binding site motif in members of the DBP family may form part of a conserved erythrocyte receptor binding pocket.</p