Comparison of the structure of vMIP-II with eotaxin-1, RANTES, and MCP-3 suggests a unique mechanism for CCR3 activation.
Herpesvirus-8 macrophage inflammatory protein-II (vMIP-II) binds a uniquely wide spectrum of chemokine receptors. We report the X-ray structure of vMIP-II determined to 2.1 A resolution. Like RANTES, vMIP-II crystallizes as a dimer and displays the conventional chemokine tertiary fold. We have compared the surface topology and electrostatic potential of vMIP-II to those of eotaxin-1, RANTES, and MCP-3, three CCR3 physiological agonists with known three-dimensional structures. Surface epitopes identified on RANTES to be involved in binding to CCR3 are mimicked on the eotaxin-1 and MCP-3 surface. However, the surface topology of vMIP-II in these regions is markedly different. The results presented here indicate that the structural basis for interaction with the chemokine receptor CCR3 by vMIP-II is different from that for the physiological agonists eotaxin-1, RANTES, and MCP-3. These differences on vMIP-II may be a consequence of its broad-range receptor recognition capabilities.
Fernandez
E J
EJ
Department of Pharmacology, Yale University School of Medicine, New Haven, Connecticut 06520, USA.
Wilken
J
J
Thompson
D A
DA
Peiper
S C
SC
Lolis
E
E
D000595:Amino Acid Sequence; D019380:Anti-HIV Agents / Q000737:chemistry*; D054413:Chemokine CCL11; D018946:Chemokine CCL5 / Q000737:chemistry*; D054410:Chemokine CCL7; D018925:Chemokines / Q000737:chemistry*; D019742:Chemokines, CC / Q000737:chemistry*; D002631:Chemotactic Factors, Eosinophil / Q000737:chemistry*; D018360:Crystallography, X-Ray; D016207:Cytokines / Q000737:chemistry*; D019288:Herpesvirus 8, Human / Q000378:metabolism; D006801:Humans; D008958:Models, Molecular; D008969:Molecular Sequence Data; D018945:Monocyte Chemoattractant Proteins / Q000737:chemistry*; D054397:Receptors, CCR3; D019707:Receptors, Chemokine / Q000378:metabolism*; D011991:Receptors, Virus / Q000378:metabolism; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
D019380:Anti-HIV Agents; C515456:CCL11 protein, human; C515450:CCL7 protein, human; C515350:CCR3 protein, human; D054413:Chemokine CCL11; D018946:Chemokine CCL5; D054410:Chemokine CCL7; D018925:Chemokines; D019742:Chemokines, CC; D002631:Chemotactic Factors, Eosinophil; D016207:Cytokines; D018945:Monocyte Chemoattractant Proteins; D054397:Receptors, CCR3; D019707:Receptors, Chemokine; D011991:Receptors, Virus; C108059:vMIP-II