[Molecular basis and structure-activity relationships of the Duffy blood group antigens: chemokine and Plasmodium vivax receptors].
Duffy blood group antigens are of major interest in clinical medicine as they are not only involved in blood transfusion risks and occasionally in neonatal hemolytic disease, but also in the invasion of red blood cells by the hemoparasitic Plasmodium vivax. The FY locus maps to chromosome 1q22-q23, and is composed of 4 alleles: FY*A and FY*B (coding for the Fya and Fyb antigens, respectively), FY*X and FY*Fy. The Duffy antigens are carried by a 336 amino-acid glycoprotein named the Duffy Antigen/Receptor for Chemokines (DARC) that can bind with high affinity selected members of the CXC and CC classes of chemokines. Today, the genetic bases of the Duffy system have been characterized. The identification of the polymorphisms associated with the 4 alleles FY*A, FY*B, FY*Fy and FY*X has led to the development of a complete genotyping of the Duffy system by PCR, which increases the safety and lessens the risk of blood transfusion, and is useful in determining feto-maternal incompatibilities and in genetic filiation analyses. DARC is not solely expressed in erythroid cells: the same polypeptide isoform is found on the surface of endothelial cells of post-capillary venules throughout the body and also on the surface of Purkinje cells in the cerebellum, although it is encoded by different RNA messengers in each case, i.e., 1.35 and 7.5 kb, respectively. The preliminary analyses of receptor-ligand interaction have shown the existence of a chemokine-binding pocket defined by the close proximity of the first and fourth transmembrane domains of the DARC protein, and also by the importance of the N-terminal extracellular region for the binding of Plasmodium vivax merozoites.
Tournamille
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Institut national de la transfusion sanguine, Paris, France.
D000483:Alleles; D019943:Amino Acid Substitution; D000818:Animals; D000953:Antigens, Protozoan; D001787:Blood Group Incompatibility / Q000209:etiology; D001803:Blood Transfusion; D002352:Carrier Proteins / Q000737:chemistry / Q000502:physiology*; D002478:Cells, Cultured; D019742:Chemokines, CC / Q000378:metabolism; D019743:Chemokines, CXC / Q000378:metabolism; D002522:Chlorocebus aethiops; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D004375:Duffy Blood-Group System / Q000737:chemistry / Q000502:physiology*; D004730:Endothelium, Vascular / Q000378:metabolism; D004912:Erythrocytes / Q000469:parasitology; D005787:Gene Frequency; D005838:Genotype; D006801:Humans; D008958:Models, Molecular; D009419:Nerve Tissue Proteins / Q000737:chemistry / Q000502:physiology; D009928:Organ Specificity; D010641:Phenotype; D010966:Plasmodium vivax / Q000502:physiology*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D012150:Polymorphism, Restriction Fragment Length; D011487:Protein Conformation; D017434:Protein Structure, Tertiary; D015800:Protozoan Proteins; D011689:Purkinje Cells / Q000378:metabolism; D044469:Racial Groups / Q000235:genetics; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000502:physiology*; D019707:Receptors, Chemokine / Q000737:chemistry / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000737:chemistry; D013329:Structure-Activity Relationship
C473745:ACKR1 protein, human; D000953:Antigens, Protozoan; D002352:Carrier Proteins; D019742:Chemokines, CC; D019743:Chemokines, CXC; D004375:Duffy Blood-Group System; C066001:Duffy antigen binding protein, Plasmodium; D009419:Nerve Tissue Proteins; D015800:Protozoan Proteins; D011956:Receptors, Cell Surface; D019707:Receptors, Chemokine; D011993:Recombinant Fusion Proteins