title: Sequence, evolution and ligand binding properties of mammalian Duffy antigen/receptor for chemokines.
abstract: The Duffy antigen/ receptor for chemokine, DARC, acts as a widely expressed promiscuous chemokine receptor and as the erythrocyte receptor for Plasmodium vivax. To gain insight into the evolution and structure/function relations of DARC, we analyzed the binding of anti-human Fy monoclonal antibodies (mAbs) and human chemokines to red blood cells (RBCs) from 11 nonhuman primates and two nonprimate mammals, and we elucidated the structures of the DARC genes from gorilla, gibbon, baboon, marmoset, tamarin, night monkey and cattle. CXCL-8 and CCL-5 chemokine binding analysis indicated that the promiscuous binding profile characteristic of DARC is conserved across species. Among three mAbs that detected the Fy6 epitope by flow cytometric analysis of human and chimpanzee RBCs, only one reacted with night monkey and squirrel monkey. Only chimpanzee RBCs bound a significant amount of the anti-Fy3 mAb. Fy3 was also poorly detected on RBCs from gorilla, baboon and rhesus monkey, but not from new world monkeys. Alignment of DARC homologous sequences allowed us to construct a phylogenetic tree in which all branchings were in accordance with current knowledge of primate phylogeny. Although DARC was expected to be under strong internal and external selection pressure, in order to maintain chemokine binding and avoid Plasmodium vivax binding, respectively, our present study did not provide arguments in favor of a selection pressure on the extracellular domains involved in ligand specificity. The amino acid variability of DARC-like polypeptides was found to be well correlated with the hydrophilicity indexes, with the highest divergence on the amino-terminal extracellular domain. Analysis of the deduced amino acid sequences highlighted the conservation of some amino acid residues, which should prove to be critical for the structural and functional properties of DARC.
authors.affiliation: INSERM U76, Institut National de la Transfusion Sanguine, 6 rue Alexandre Cabanel, 75015, Paris, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Tournamille
authors.forename: Antoine
authors.initials: A
authors.lastname: Blancher
authors.forename: Caroline
authors.initials: C
authors.lastname: Le Van Kim
authors.forename: Pierre
authors.initials: P
authors.lastname: Gane
authors.forename: Pol André
authors.initials: PA
authors.lastname: Apoil
authors.forename: Wilson
authors.initials: W
authors.lastname: Nakamoto
authors.forename: Jean Pierre
authors.initials: JP
authors.lastname: Cartron
authors.forename: Yves
authors.initials: Y
authors.lastname: Colin
mesh_terms: D000818:Animals; D002417:Cattle / Q000235:genetics; D006801:Humans; D051379:Mice; D000595:Amino Acid Sequence; D000911:Antibodies, Monoclonal / Q000276:immunology; D000953:Antigens, Protozoan / Q000378:metabolism; D001483:Base Sequence; D001665:Binding Sites; D001789:Blood Group Antigens; D018946:Chemokine CCL5; D019742:Chemokines, CC / Q000378:metabolism; D019743:Chemokines, CXC / Q000378:metabolism; D004375:Duffy Blood-Group System / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D000939:Epitopes / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D004912:Erythrocytes / Q000378:metabolism; D019143:Evolution, Molecular; D057927:Hydrophobic and Hydrophilic Interactions; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D008024:Ligands; D008969:Molecular Sequence Data; D010802:Phylogeny; D011323:Primates / Q000235:genetics; D011485:Protein Binding; D015800:Protozoan Proteins / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D012641:Selection, Genetic; D016415:Sequence Alignment; D017385:Sequence Homology; D013045:Species Specificity
chemical_list: C473745:ACKR1 protein, human; D000911:Antibodies, Monoclonal; D000953:Antigens, Protozoan; D001789:Blood Group Antigens; C483024:CCL5 protein, human; D018946:Chemokine CCL5; D019742:Chemokines, CC; D019743:Chemokines, CXC; C066001:Duffy antigen binding protein, Plasmodium; D004375:Duffy Blood-Group System; D000939:Epitopes; D036341:Intercellular Signaling Peptides and Proteins; D008024:Ligands; D015800:Protozoan Proteins; D011956:Receptors, Cell Surface; C483025:Ackr1 protein mouse