The domain on the Duffy blood group antigen for binding Plasmodium vivax and P. knowlesi malarial parasites to erythrocytes.
Plasmodium vivax and the related simian malarial parasite P. knowlesi use the Duffy blood group antigen as a receptor to invade human erythrocytes and region II of the parasite ligands for binding to this erythrocyte receptor. Here, we identify the peptide within the Duffy blood group antigen of human and rhesus erythrocytes to which the P. vivax and P. knowlesi ligands bind. Peptides from the NH2-terminal extracellular region of the Duffy antigen were tested for their ability to block the binding of erythrocytes to transfected Cos cells expressing on their surface region II of the Duffy-binding ligands. The binding site on the human Duffy antigen used by both the P. vivax and P. knowlesi ligands maps to a 35-amino acid region. A 34-amino acid peptide from the equivalent region of the rhesus Duffy antigen blocked the binding of P. vivax to human erythrocytes, although the P. vivax ligand expressed on Cos cells does not bind rhesus erythrocytes. The binding of the rhesus peptide, but not the rhesus erythrocyte, to the P. vivax ligand was explained by interference of carbohydrate with the binding process. Rhesus erythrocytes, treated with N-glycanase, bound specifically to P. vivax region II. Thus, the interaction of P. vivax ligand with human and rhesus erythrocytes appears to be mediated by a peptide-peptide interaction. Glycosylation of the rhesus Duffy antigen appears to block binding of the P. vivax ligand to rhesus erythrocytes.
Chitnis
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CE
Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA.
Chaudhuri
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A
Horuk
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R
Pogo
A O
AO
Miller
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LH
D000581:Amidohydrolases / Q000494:pharmacology; D000595:Amino Acid Sequence; D000818:Animals; D000953:Antigens, Protozoan; D001667:Binding, Competitive; D002352:Carrier Proteins / Q000276:immunology* / Q000378:metabolism; D054360:Chemokine CXCL1; D019743:Chemokines, CXC; D002630:Chemotactic Factors / Q000494:pharmacology; D004375:Duffy Blood-Group System / Q000276:immunology*; D000939:Epitopes; D004912:Erythrocytes / Q000276:immunology* / Q000469:parasitology; D006131:Growth Inhibitors / Q000494:pharmacology; D006133:Growth Substances / Q000494:pharmacology; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D008253:Macaca mulatta; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism / Q000494:pharmacology; D043524:Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase; D010961:Plasmodium / Q000276:immunology*; D016790:Plasmodium knowlesi / Q000276:immunology; D010966:Plasmodium vivax / Q000276:immunology; D011485:Protein Binding / Q000187:drug effects; D015800:Protozoan Proteins; D011956:Receptors, Cell Surface / Q000276:immunology* / Q000378:metabolism; D013045:Species Specificity
D000953:Antigens, Protozoan; C475829:CXCL1 protein, human; D002352:Carrier Proteins; D054360:Chemokine CXCL1; D019743:Chemokines, CXC; D002630:Chemotactic Factors; D004375:Duffy Blood-Group System; C066001:Duffy antigen binding protein, Plasmodium; D000939:Epitopes; D006131:Growth Inhibitors; D006133:Growth Substances; D036341:Intercellular Signaling Peptides and Proteins; D010446:Peptide Fragments; D015800:Protozoan Proteins; D011956:Receptors, Cell Surface; D000581:Amidohydrolases; D043524:Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase