The cytomegalovirus US28 protein binds multiple CC chemokines with high affinity.
Human cytomegalovirus encodes several proteins with high similarity to seven transmembrane domain receptors. We investigated the ability of one of these proteins, the product of the US28 open reading frame, to bind various chemoattractant ligands. When transfected into COS-7 cells, the US28 product conferred high affinity binding to the labeled chemokines monocyte chemoattractant protein-1 (MCP-1) (Kd = 6.0 x 10(-10) M) and RANTES (Kd = 2.7 x 10(-10) M). Binding of these labeled ligands could be competed by the unlabeled macrophage inflammatory proteins MIP-1 alpha and MIP-1 beta, with Kd values in the range 1.2 x 10(-9) to 7.5 x 10(-9) M. Comparisons of the sequences of US28 and other receptors that bind chemokines should help to define regions responsible for receptor-ligand interactions.
Kuhn
D E
DE
Ohio State University, Neurobiotechnology Center, Columbus 43210, USA.
Beall
C J
CJ
Kolattukudy
P E
PE
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D002630:Chemotactic Factors / Q000378:metabolism*; D002522:Chlorocebus aethiops; D016207:Cytokines / Q000378:metabolism*; D003587:Cytomegalovirus / Q000378:metabolism*; D017931:DNA Primers; D007668:Kidney; D007700:Kinetics; D008222:Lymphokines / Q000378:metabolism*; D019402:Macrophage Inflammatory Proteins; D008969:Molecular Sequence Data; D018945:Monocyte Chemoattractant Proteins; D015846:Monokines / Q000378:metabolism*; D016366:Open Reading Frames; D011485:Protein Binding; D054390:Receptors, CCR2; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine / Q000378:metabolism*; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000378:metabolism; D014162:Transfection
C515334:CCR2 protein, human; D054407:Chemokine CCL4; D018946:Chemokine CCL5; D002630:Chemotactic Factors; D016207:Cytokines; D017931:DNA Primers; D008222:Lymphokines; D019402:Macrophage Inflammatory Proteins; D018945:Monocyte Chemoattractant Proteins; D015846:Monokines; D054390:Receptors, CCR2; D019707:Receptors, Chemokine; D018121:Receptors, Cytokine; D011994:Recombinant Proteins