About this Journal Submit a Manuscript Table of Contents
Advances in Virology
Volume 2012 (2012), Article ID 231813, 15 pages
http://dx.doi.org/10.1155/2012/231813
Review Article

Structural Diversity in Conserved Regions Like the DRY-Motif among Viral 7TM Receptors—A Consequence of Evolutionary Pressure?

1Laboratory for Molecular Pharmacology, Department of Neuroscience and Pharmacology, The Panum Institute, University of Copenhagen, Building 18.5, Blegdamsvej 3, 2200-Copenhagen N, Denmark
2Sir Albert Sakzewski Virus Research Centre (SASVRC), Royal Children's Hospital/Clinical Medical Virology Centre (CMVC), University of Queensland, St Lucia, QLD 4072, Australia

Received 15 March 2012; Accepted 31 May 2012

Academic Editor: Rika Draenert

Copyright © 2012 Ann-Sofie Mølleskov Jensen et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Linked References

  1. D. M. Rosenbaum, S. G. F. Rasmussen, and B. K. Kobilka, “The structure and function of G-protein-coupled receptors,” Nature, vol. 459, no. 7245, pp. 356–363, 2009. View at Publisher · View at Google Scholar · View at Scopus
  2. K. Rajagopal, R. J. Lefkowitz, and H. A. Rockman, “When 7 transmembrane receptors are not G protein-coupled receptors,” Journal of Clinical Investigation, vol. 115, no. 11, pp. 2971–2974, 2005. View at Publisher · View at Google Scholar · View at Scopus
  3. T. M. Cabrera-Vera, et al., “Insights into G protein structure, function, and regulation,” Endocrine Reviews, vol. 24, no. 6, pp. 765–781, 2003.
  4. R. J. Lefkowitz, “Seven transmembrane receptors: something old, something new,” Acta Physiologica, vol. 190, no. 1, pp. 9–19, 2007. View at Publisher · View at Google Scholar · View at Scopus
  5. C. Altenbach, A. K. Kusnetzow, O. P. Ernst, K. P. Hofmann, and W. L. Hubbell, “High-resolution distance mapping in rhodopsin reveals the pattern of helix movement due to activation,” Proceedings of the National Academy of Sciences of the United States of America, vol. 105, no. 21, pp. 7439–7444, 2008. View at Publisher · View at Google Scholar · View at Scopus
  6. W. L. Hubbell, C. Altenbach, C. M. Hubbell, and H. G. Khorana, “Rhodopsin structure, dynamics, and activation: a perspective from crystallography, site-directed spin labeling, sulfhydryl reactivity, and disulfide cross-linking,” Advances in Protein Chemistry, vol. 63, pp. 243–290, 2003. View at Publisher · View at Google Scholar · View at Scopus
  7. T. W. Schwartz, T. M. Frimurer, B. Holst, M. M. Rosenkilde, and C. E. Elling, “Molecular mechanism of 7tm receptor activation—a global toggle switch model,” Annual Review of Pharmacology and Toxicology, vol. 46, pp. 481–519, 2006. View at Publisher · View at Google Scholar · View at Scopus
  8. T. W. Schwartz, “Locating ligand-binding sites in 7tm receptors by protein engineering,” Current Opinion in Biotechnology, vol. 5, no. 4, pp. 434–444, 1994. View at Publisher · View at Google Scholar · View at Scopus
  9. J. A. Ballesteros and H. Weinstein, “Integrated methods for the construction of three-dimensional models and computational probing of structure-function relations in G protein-coupled receptors,” in Receptor molecular biology, S. C. Sealfon, Ed., Academic Press, New York, NY, USA, 1995.
  10. K. Palczewski, T. Kumasaka, T. Hori et al., “Crystal structure of rhodopsin: a G protein-coupled receptor,” Science, vol. 289, no. 5480, pp. 739–745, 2000. View at Publisher · View at Google Scholar · View at Scopus
  11. V. Cherezov, D. M. Rosenbaum, M. A. Hanson et al., “High-resolution crystal structure of an engineered human β2-adrenergic G protein-coupled receptor,” Science, vol. 318, no. 5854, pp. 1258–1265, 2007. View at Publisher · View at Google Scholar · View at Scopus
  12. T. Warne, et al., “Structure of a beta1-adrenergic G-protein-coupled receptor,” Nature, no. 7203, pp. 486–491, 2008.
  13. S. G. F. Rasmussen, H. J. Choi, J. J. Fung et al., “Structure of a nanobody-stabilized active state of the β2 adrenoceptor,” Nature, vol. 469, no. 7329, pp. 175–180, 2011. View at Publisher · View at Google Scholar · View at Scopus
  14. S. G. Rasmussen, et al., “Crystal structure of the beta 2 adrenergic receptor-Gs protein complex,” Nature, vol. 477, no. 7366, pp. 549–555, 2011. View at Publisher · View at Google Scholar
  15. S. G. Rasmussen, et al., “Crystal structure of the human beta2 adrenergic G-protein-coupled receptor,” Nature, vol. 450, no. 7168, pp. 383–387, 2007.
  16. A. S. Dore, et al., “Structure of the adenosine A(2A) receptor in complex with ZM241385 and the xanthines XAC and caffeine,” Structure, vol. 19, no. 9, pp. 1283–1293, 2011.
  17. G. Lebon, T. Warne, P. C. Edwards et al., “Agonist-bound adenosine A2A receptor structures reveal common features of GPCR activation,” Nature, vol. 474, no. 7352, pp. 521–525, 2011. View at Publisher · View at Google Scholar · View at Scopus
  18. F. Xu, H. Wu, V. Katritch et al., “Structure of an agonist-bound human A2A adenosine receptor,” Science, vol. 332, no. 6027, pp. 322–327, 2011. View at Publisher · View at Google Scholar · View at Scopus
  19. H. W. Choe, Y. J. Kim, J. H. Park et al., “Crystal structure of metarhodopsin II,” Nature, vol. 471, no. 7340, pp. 651–655, 2011. View at Publisher · View at Google Scholar · View at Scopus
  20. J. Standfuss, P. C. Edwards, A. D'Antona et al., “The structural basis of agonist-induced activation in constitutively active rhodopsin,” Nature, vol. 471, no. 7340, pp. 656–660, 2011. View at Publisher · View at Google Scholar · View at Scopus
  21. P. Scheerer, J. H. Park, P. W. Hildebrand et al., “Crystal structure of opsin in its G-protein-interacting conformation,” Nature, vol. 455, no. 7212, pp. 497–502, 2008. View at Publisher · View at Google Scholar · View at Scopus
  22. K. Haga, A. C. Kruse, H. Asada et al., “Structure of the human M2 muscarinic acetylcholine receptor bound to an antagonist,” Nature, vol. 482, no. 7386, pp. 547–551, 2012. View at Publisher · View at Google Scholar · View at Scopus
  23. A. C. Kruse, J. Hu, A. C. Pan et al., “Structure and dynamics of the M3 muscarinic acetylcholine receptor,” Nature, vol. 482, no. 7386, pp. 552–556, 2012. View at Publisher · View at Google Scholar · View at Scopus
  24. E. Y. T. Chien, W. Liu, Q. Zhao et al., “Structure of the human dopamine D3 receptor in complex with a D2/D3 selective antagonist,” Science, vol. 330, no. 6007, pp. 1091–1095, 2010. View at Publisher · View at Google Scholar · View at Scopus
  25. M. A. Hanson, C. B. Roth, E. Jo et al., “Crystal structure of a lipid G protein-coupled receptor,” Science, vol. 335, no. 6070, pp. 851–855, 2012. View at Publisher · View at Google Scholar · View at Scopus
  26. T. Shimamura, et al., “Structure of the human histamine H1 receptor complex with doxepin,” Nature, vol. 475, no. 7354, pp. 65–70, 2011. View at Publisher · View at Google Scholar
  27. B. Wu, E. Y. T. Chien, C. D. Mol et al., “Structures of the CXCR4 chemokine GPCR with small-molecule and cyclic peptide antagonists,” Science, vol. 330, no. 6007, pp. 1066–1071, 2010. View at Publisher · View at Google Scholar · View at Scopus
  28. J. H. Park, P. Scheerer, K. P. Hofmann, H. W. Choe, and O. P. Ernst, “Crystal structure of the ligand-free G-protein-coupled receptor opsin,” Nature, vol. 454, no. 7201, pp. 183–187, 2008. View at Publisher · View at Google Scholar · View at Scopus
  29. V. P. Jaakola, M. T. Griffith, M. A. Hanson et al., “The 2.6 angstrom crystal structure of a human A2A adenosine receptor bound to an antagonist,” Science, vol. 322, no. 5905, pp. 1211–1217, 2008. View at Publisher · View at Google Scholar · View at Scopus
  30. R. Nygaard, T. M. Frimurer, B. Holst, M. M. Rosenkilde, and T. W. Schwartz, “Ligand binding and micro-switches in 7tm receptor structures,” Trends in Pharmacological Sciences, vol. 30, no. 5, pp. 249–259, 2009. View at Publisher · View at Google Scholar · View at Scopus
  31. T. Mirzadegan, G. Benko, S. Filipek, and K. Palczewski, “Sequence analyses of G-protein-coupled receptors: similarities to rhodopsin,” Biochemistry, vol. 42, no. 10, pp. 2759–2767, 2003. View at Publisher · View at Google Scholar · View at Scopus
  32. M. M. Rosenkilde, T. Benned-Jensen, T. M. Frimurer, and T. W. Schwartz, “The minor binding pocket: a major player in 7tm receptor activation,” Trends in Pharmacological Sciences, vol. 31, no. 12, pp. 567–574, 2010. View at Publisher · View at Google Scholar · View at Scopus
  33. T. Benned-Jensen and M. M. Rosenkilde, “Structural motifs of importance for the constitutive activity of the orphan 7tm receptor EBI2: analysis of receptor activation in the absence of an agonist,” Molecular Pharmacology, vol. 74, no. 4, pp. 1008–1021, 2008. View at Publisher · View at Google Scholar · View at Scopus
  34. T. Benned-Jensen and M. M. Rosenkilde, “The role of transmembrane segment II in 7tm receptor activation,” Current Molecular Pharmacology, vol. 2, no. 2, pp. 140–148, 2009. View at Publisher · View at Google Scholar · View at Scopus
  35. T. W. Schwartz and T. P. Sakmar, “Structural biology: snapshot of a signalling complex,” Nature, vol. 477, no. 7366, pp. 540–541, 2011. View at Publisher · View at Google Scholar · View at Scopus
  36. J. A. Ballesteros, A. D. Jensen, G. Liapakis et al., “Activation of the beta 2-adrenergic receptor involves disruption of an ionic lock between the cytoplasmic ends of transmembrane segments 3 and 6,” Journal of Biological Chemistry, vol. 276, no. 31, pp. 29171–29177, 2001. View at Publisher · View at Google Scholar · View at Scopus
  37. D. M. Rosenbaum, C. Zhang, J. A. Lyons et al., “Structure and function of an irreversible agonist-β2 adrenoceptor complex,” Nature, vol. 469, no. 7329, pp. 236–240, 2011. View at Publisher · View at Google Scholar · View at Scopus
  38. J. Y. Springael, C. de Poorter, X. Deupi, J. Van Durme, L. Pardo, and M. Parmentier, “The activation mechanism of chemokine receptor CCR5 involves common structural changes but a different network of interhelical interactions relative to rhodopsin,” Cellular Signalling, vol. 19, no. 7, pp. 1446–1456, 2007. View at Publisher · View at Google Scholar · View at Scopus
  39. K. N. Nobles, K. Xiao, S. Ahn et al., “Distinct phosphorylation sites on the β2-adrenergic receptor establish a barcode that encodes differential functions of β-arrestin,” Science Signaling, vol. 4, no. 185, Article ID ra51, 2011. View at Publisher · View at Google Scholar · View at Scopus
  40. M. M. Rosenkilde and N. Kledal, “Targeting herpesvirus reliance of the chemokine system,” Current Drug Targets, vol. 7, no. 1, pp. 103–118, 2006. View at Publisher · View at Google Scholar · View at Scopus
  41. M. M. Rosenkilde, “Virus-encoded chemokine receptors—putative novel antiviral drug targets,” Neuropharmacology, vol. 48, no. 1, pp. 1–13, 2005. View at Publisher · View at Google Scholar · View at Scopus
  42. P. M. Murphy, “Viral exploitation and subversion of the immune system through chemokine mimicry,” Nature Immunology, vol. 2, no. 2, pp. 116–122, 2001. View at Publisher · View at Google Scholar · View at Scopus
  43. M. M. Rosenkilde and T. W. Schwartz, “Glu VII:06—a highly conserved and selective anchor point for non-peptide ligands in chemokine receptors,” Current Topics in Medicinal Chemistry, vol. 6, no. 13, pp. 1319–1333, 2006. View at Scopus
  44. P. M. Murphy, M. Baggiolini, I. F. Charo et al., “International union of pharmacology. XXII. Nomenclature for chemokine receptors,” Pharmacological Reviews, vol. 52, no. 1, pp. 145–176, 2000. View at Scopus
  45. P. M. Murphy, “International union of pharmacology. XXX. Update on chemokine receptor nomenclature,” Pharmacological Reviews, vol. 54, no. 2, pp. 227–229, 2002. View at Publisher · View at Google Scholar · View at Scopus
  46. R. M. Strieter, P. J. Polverini, S. L. Kunkel et al., “The functional role of the ELR motif in CXC chemokine-mediated angiogenesis,” Journal of Biological Chemistry, vol. 270, no. 45, pp. 27348–27357, 1995. View at Publisher · View at Google Scholar · View at Scopus
  47. M. M. Rosenkilde and T. W. Schwartz, “The chemokine system—a major regulator of angiogenesis in health and disease,” APMIS, vol. 112, no. 7-8, pp. 481–495, 2004. View at Publisher · View at Google Scholar · View at Scopus
  48. P. J. Holst and M. M. Rosenkilde, “Microbiological exploitation of the chemokine system,” Microbes and Infection, vol. 5, no. 2, pp. 179–187, 2003. View at Publisher · View at Google Scholar · View at Scopus
  49. E. R. Neptune and H. R. Bourne, “Receptors induce chemotaxis by releasing the βγ subunit of Gi, not by activating Gq or Gs,” Proceedings of the National Academy of Sciences of the United States of America, vol. 94, no. 26, pp. 14489–14494, 1997. View at Scopus
  50. M. M. Rosenkilde, M. Waldhoer, H. R. Lüttichau, and T. W. Schwartz, “Virally encoded 7tm receptors,” Oncogene, vol. 20, no. 13, pp. 1582–1593, 2001. View at Publisher · View at Google Scholar · View at Scopus
  51. H. Choe, K. A. Martin, M. Farzan, J. Sodroski, N. P. Gerard, and C. Gerard, “Structural interactions between chemokine receptors, gp120 Env and CD4,” Seminars in Immunology, vol. 10, no. 3, pp. 249–257, 1998. View at Publisher · View at Google Scholar · View at Scopus
  52. O. Pleskoff, C. Tréboute, A. Brelot, N. Heveker, M. Seman, and M. Alizon, “Identification of a chemokine receptor encoded by human cytomegalovirus as a cofactor for HIV-1 entry,” Science, vol. 276, no. 5320, pp. 1874–1878, 1997. View at Publisher · View at Google Scholar · View at Scopus
  53. M. M. Rosenkilde, M. J. Smit, and M. Waldhoer, “Structure, function and physiological consequences of virally encoded chemokine seven transmembrane receptors,” British Journal of Pharmacology, vol. 153, supplement 1, pp. S154–S166, 2008. View at Publisher · View at Google Scholar · View at Scopus
  54. M. Waldhoer, T. N. Kledal, H. Farrell, and T. W. Schwartz, “Murine cytomegalovirus (CMV) M33 and human CMV US28 receptors exhibit similar constitutive signaling activities,” Journal of Virology, vol. 76, no. 16, pp. 8161–8168, 2002. View at Publisher · View at Google Scholar · View at Scopus
  55. M. M. Rosenkilde, T. N. Kledal, and T. W. Schwartz, “High constitutive activity of a virus-encoded seven transmembrane receptor in the absence of the conserved DRY motif (Asp-Arg-Tyr) in transmembrane helix 3,” Molecular Pharmacology, vol. 68, no. 1, pp. 11–19, 2005. View at Publisher · View at Google Scholar · View at Scopus
  56. M. J. Smit, D. Verzijl, P. Casarosa, M. Navis, H. Timmerman, and R. Leurs, “Kaposi's sarcoma-associated herpesvirus-encoded G protein-coupled receptor ORF74 constitutively activates p44/p42 MAPK and Akt via Gi and phospholipase C-dependent signaling pathways,” Journal of Virology, vol. 76, no. 4, pp. 1744–1752, 2002. View at Publisher · View at Google Scholar · View at Scopus
  57. K. A. McLean, P. J. Holst, L. Martini, T. W. Schwartz, and M. M. Rosenkilde, “Similar activation of signal transduction pathways by the herpesvirus-encoded chemokine receptors US28 and ORF74,” Virology, vol. 325, no. 2, pp. 241–251, 2004. View at Publisher · View at Google Scholar · View at Scopus
  58. R. Seifert and K. Wenzel-Seifert, “Constitutive activity of G-proteins-coupled receptors: cause of disease and common property of wild-type receptors,” Naunyn-Schmiedeberg's Archives of Pharmacology, vol. 366, no. 5, pp. 381–416, 2002. View at Publisher · View at Google Scholar · View at Scopus
  59. L. S. Robbins, J. H. Nadeau, K. R. Johnson et al., “Pigmentation phenotypes of variant extension locus alleles result from point mutations that alter MSH receptor function,” Cell, vol. 72, no. 6, pp. 827–834, 1993. View at Publisher · View at Google Scholar · View at Scopus
  60. S. Srinivasan, C. Lubrano-Berthelier, C. Govaerts et al., “Constitutive activity of the melanocortin-4 receptor is maintained by its N-terminal domain and plays a role in energy homeostasis in humans,” Journal of Clinical Investigation, vol. 114, no. 8, pp. 1158–1164, 2004. View at Publisher · View at Google Scholar · View at Scopus
  61. J. Pantel, M. Legendre, S. Cabrol et al., “Loss of constitutive activity of the growth hormone secretagogue receptor in familial short stature,” Journal of Clinical Investigation, vol. 116, no. 3, pp. 760–768, 2006. View at Publisher · View at Google Scholar · View at Scopus
  62. P. R. Robinson, G. B. Cohen, E. A. Zhukovsky, and D. D. Oprian, “Constitutively active mutants of rhodopsin,” Neuron, vol. 9, no. 4, pp. 719–725, 1992. View at Publisher · View at Google Scholar · View at Scopus
  63. M. M. Rosenkilde, T. N. Kledal, H. Bräuner-Osborne, and T. W. Schwartz, “Agonists and inverse agonists for the herpesvirus 8-encoded constitutively active seven-transmembrane oncogene product, ORF-74,” Journal of Biological Chemistry, vol. 274, no. 2, pp. 956–961, 1999. View at Publisher · View at Google Scholar · View at Scopus
  64. C. Bais, B. Santomasso, O. Coso et al., “G-protein-coupled receptor of Kaposi's sarcoma-associated herpesvirus is a viral oncogene and angiogenesis activator,” Nature, vol. 391, no. 6662, pp. 86–89, 1998. View at Publisher · View at Google Scholar · View at Scopus
  65. A. Sodhi, S. Montaner, V. Patel et al., “The Kaposi's sarcoma-associated herpes virus G protein-coupled receptor up-regulates vascular endothelial growth factor expression and secretion through mitogen-activated protein kinase and p38 pathways acting on hypoxia-inducible factor 1α,” Cancer Research, vol. 60, no. 17, pp. 4873–4880, 2000. View at Scopus
  66. S. Montaner, A. Sodhi, S. Pece, E. A. Mesri, and J. S. Gutkind, “The Kaposi's sarcoma-associated herpesvirus G protein-coupled receptor promotes endothelial cell survival through the activation of Akt/protein kinase B,” Cancer Research, vol. 61, no. 6, pp. 2641–2648, 2001. View at Scopus
  67. S. Montaner, A. Sodhi, A. Molinolo et al., “Endothelial infection with KSHV genes in vivo reveals that vGPCR initiates Kaposi's sarcomagenesis and can promote the tumorigenic potential of viral latent genes,” Cancer Cell, vol. 3, no. 1, pp. 23–36, 2003. View at Publisher · View at Google Scholar · View at Scopus
  68. A. Sodhi, S. Montaner, V. Patel et al., “Akt plays a central role in sarcomagenesis induced by Kaposi's sarcoma herpesvirus-encoded G protein-coupled receptor,” Proceedings of the National Academy of Sciences of the United States of America, vol. 101, no. 14, pp. 4821–4826, 2004. View at Publisher · View at Google Scholar · View at Scopus
  69. M. M. Rosenkildel, K. A. McLean, P. J. Holst, and T. W. Schwartz, “The CXC chemokine receptor encoded by herpesvirus saimiri, ECRF3, shows ligand-regulated signaling through Gi, Gq, and G 12/13 proteins but constitutive signaling only through Gi and G12/13 proteins,” Journal of Biological Chemistry, vol. 279, no. 31, pp. 32524–32533, 2004. View at Publisher · View at Google Scholar · View at Scopus
  70. S. K. Ahuja and P. M. Murphy, “Molecular piracy of mammalian interleukin-8 receptor type B by herpesvirus saimiri,” Journal of Biological Chemistry, vol. 268, no. 28, pp. 20691–20694, 1993. View at Scopus
  71. T. N. Kledal, M. M. Rosenkilde, and T. W. Schwartz, “Selective recognition of the membrane-bound CX3C chemokine, fractalkine, by the human cytomegalovirus-encoded broad-spectrum receptor US28,” FEBS Letters, vol. 441, no. 2, pp. 209–214, 1998. View at Publisher · View at Google Scholar · View at Scopus
  72. P. Casarosa, Y. K. Gruijthuijsen, D. Michel et al., “Constitutive signaling of the human cytomegalovirus-encoded receptor UL33 differs from that of its rat cytomegalovirus homolog R33 by promiscuous activation of G proteins of the Gq, Gi, and Gs classes,” Journal of Biological Chemistry, vol. 278, no. 50, pp. 50010–50023, 2003. View at Publisher · View at Google Scholar · View at Scopus
  73. P. Casarosa, R. A. Bakker, D. Verzijl et al., “Constitutive signaling of the human cytomegalovirus-encoded chemokine receptor US28,” Journal of Biological Chemistry, vol. 276, no. 2, pp. 1133–1137, 2001. View at Publisher · View at Google Scholar · View at Scopus
  74. N. J. Davis-poynter, D. M. Lynch, H. Vally et al., “Identification and characterization of a G protein-coupled receptor homolog encoded by murine cytomegalovirus,” Journal of Virology, vol. 71, no. 2, pp. 1521–1529, 1997. View at Scopus
  75. P. S. Beisser, C. Vink, J. G. van Dam, G. Grauls, S. J. V. Vanherle, and C. A. Bruggeman, “The R33 G protein-coupled receptor gene of rat cytomegalovirus plays an essential role in the pathogenesis of viral infection,” Journal of Virology, vol. 72, no. 3, pp. 2352–2363, 1998. View at Scopus
  76. A. Alcami, “Viral mimicry of cytokines, chemokines and their receptors,” Nature Reviews Immunology, vol. 3, no. 1, pp. 36–50, 2003. View at Publisher · View at Google Scholar · View at Scopus
  77. A. Alcami, “Interaction of viral chemokine inhibitors with chemokines,” Methods in Molecular Biology, vol. 239, pp. 167–180, 2004. View at Scopus
  78. P. Najarro, H. J. Lee, J. Fox, J. Pease, and G. L. Smith, “Yaba-like disease virus protein 7L is a cell-surface receptor for chemokine CCL1,” Journal of General Virology, vol. 84, pp. 3325–3336, 2003. View at Publisher · View at Google Scholar · View at Scopus
  79. P. Najarro, C. Gubser, M. Hollinshead, J. Fox, J. Pease, and G. L. Smith, “Yaba-like disease virus chemokine receptor 7L, a CCR8 orthologue,” Journal of General Virology, vol. 87, pp. 809–816, 2006. View at Publisher · View at Google Scholar · View at Scopus
  80. S. J. Paulsen, M. M. Rosenkilde, J. Eugen-Olsen, and T. N. Kledal, “Epstein-barr virus-encoded BILF1 is a constitutively active G protein-coupled receptor,” Journal of Virology, vol. 79, no. 1, pp. 536–546, 2005. View at Publisher · View at Google Scholar · View at Scopus
  81. P. S. Baisser, D. Verzijl, Y. K. Gruijthuijsen et al., “The Epstein-Barr virus BILF1 gene encodes a G protein-coupled receptor that inhibits phosphorylation of RNA-dependent protein kinase,” Journal of Virology, vol. 79, no. 1, pp. 441–449, 2005. View at Publisher · View at Google Scholar · View at Scopus
  82. M. M. Rosenkilde, T. Benned-Jensen, H. Andersen et al., “Molecular pharmacological phenotyping of EBI2: an orphan seven-transmembrane receptor with constitutive activity,” Journal of Biological Chemistry, vol. 281, no. 19, pp. 13199–13208, 2006. View at Publisher · View at Google Scholar · View at Scopus
  83. U. Gether, F. Asmar, A. K. Meinild, and S. G. F. Rasmussen, “Structural basis for activation of G-protein-coupled receptors,” Pharmacology and Toxicology, vol. 91, no. 6, pp. 304–312, 2002. View at Publisher · View at Google Scholar · View at Scopus
  84. S. G. F. Rasmussen, A. D. Jensen, G. Liapakis, P. Ghanouni, J. A. Javitch, and U. Gether, “Mutation of a highly conserved aspartic acid in the β2 adrenergic receptor: constitutive activation, structural instability, and conformational rearrangement of transmembrane segment 6,” Molecular Pharmacology, vol. 56, no. 1, pp. 175–184, 1999. View at Scopus
  85. W. M. Oldham and H. E. Hamm, “Heterotrimeric G protein activation by G-protein-coupled receptors,” Nature Reviews Molecular Cell Biology, vol. 9, no. 1, pp. 60–71, 2008. View at Publisher · View at Google Scholar · View at Scopus
  86. B. Lagane, S. Ballet, T. Planchenault et al., “Mutation of the DRY motif reveals different structural requirements for the CC chemokine receptor 5-mediated signaling and receptor endocytosis,” Molecular Pharmacology, vol. 67, no. 6, pp. 1966–1976, 2005. View at Publisher · View at Google Scholar · View at Scopus
  87. F. Hüttenrauch, A. Nitzki, F. T. Lin, S. Höning, and M. Oppermann, “β-arrestin binding to CC chemokine receptor 5 requires multiple C-terminal receptor phosphorylation sites and involves a conserved Asp-Arg-Tyr sequence motif,” Journal of Biological Chemistry, vol. 277, no. 34, pp. 30769–30777, 2002. View at Publisher · View at Google Scholar · View at Scopus
  88. E. H. Schneider, D. Schnell, A. Strasser, S. Dove, and R. Seifert, “Impact of the DRY motif and the missing “ionic lock” on constitutive activity and G-protein coupling of the human histamine H4 receptor,” Journal of Pharmacology and Experimental Therapeutics, vol. 333, no. 2, pp. 382–392, 2010. View at Publisher · View at Google Scholar · View at Scopus
  89. K. Takahashi, S. Tokita, and H. Kotani, “Generation and characterization of highly constitutive active histamine H3 receptors,” Journal of Pharmacology and Experimental Therapeutics, vol. 307, no. 1, pp. 213–218, 2003. View at Publisher · View at Google Scholar · View at Scopus
  90. A. Rouleau, X. Ligneau, J. Tardivel-Lacombe et al., “Histamine H3-receptor-mediated [35S]GTPγ[S] binding: evidence for constitutive activity of the recombinant and native rat and human H3 receptors,” British Journal of Pharmacology, vol. 135, no. 2, pp. 383–392, 2002. View at Scopus
  91. K. Kristiansen, “Molecular mechanisms of ligand binding, signaling, and regulation within the superfamily of G-protein-coupled receptors: molecular modeling and mutagenesis approaches to receptor structure and function,” Pharmacology and Therapeutics, vol. 103, no. 1, pp. 21–80, 2004. View at Publisher · View at Google Scholar · View at Scopus
  92. A. E. Alewijnse, H. Timmerman, E. H. Jacobs et al., “The effect of mutations in the DRY motif on the constitutive activity and structural instability of the histamine H2 receptor,” Molecular Pharmacology, vol. 57, no. 5, pp. 890–898, 2000. View at Scopus
  93. S. Okinaga, D. Slattery, A. Humbles et al., “C5L2, a nonsignaling C5A binding protein,” Biochemistry, vol. 42, no. 31, pp. 9406–9415, 2003. View at Publisher · View at Google Scholar · View at Scopus
  94. S. C. Peiper, Z. X. Wang, K. Neote et al., “The duffy antigen/receptor for chemokines (DARC) is expressed in endothelial cells of duffy negative individuals who lack the erythrocyte receptor,” Journal of Experimental Medicine, vol. 181, no. 4, pp. 1311–1317, 1995. View at Publisher · View at Google Scholar · View at Scopus
  95. M. Pruenster and A. Rot, “Throwing light on DARC,” Biochemical Society Transactions, vol. 34, pp. 1005–1008, 2006. View at Publisher · View at Google Scholar · View at Scopus
  96. R. J. B. Nibbs, S. M. Wylie, J. Yang, N. R. Landau, and G. J. Graham, “Cloning and characterization of a novel promiscuous human β-chemokine receptor D6,” Journal of Biological Chemistry, vol. 272, no. 51, pp. 32078–32083, 1997. View at Publisher · View at Google Scholar · View at Scopus
  97. M. Weber, E. Blair, C. V. Simpson et al., “The chemokine receptor D6 constitutively traffics to and from the cell surface to internalize and degrade chemokines,” Molecular Biology of the Cell, vol. 15, no. 5, pp. 2492–2508, 2004. View at Publisher · View at Google Scholar · View at Scopus
  98. P. J. Holst, H. R. Lüttichau, T. W. Schwartz, and M. M. Rosenkilde, “Virally encoded chemokines and chemokine receptors in the role of viral infections,” Contributions to Microbiology, vol. 10, pp. 232–252, 2003. View at Scopus
  99. C. A. Flanagan, “A GPCR that is not ‘DRY’,” Molecular Pharmacology, vol. 68, no. 1, pp. 1–3, 2005. View at Publisher · View at Google Scholar · View at Scopus
  100. L. Arvanitakis, E. Geras-Raaka, A. Varma, M. C. Gershengorn, and E. Cesarman, “Human herpesvirus KSHV encodes a constitutively active G-protein- coupled receptor linked to cell proliferation,” Nature, vol. 385, no. 6614, pp. 347–350, 1997. View at Publisher · View at Google Scholar · View at Scopus
  101. M. Burger, J. A. Burger, R. C. Hoch, Z. Oades, H. Takamori, and I. U. Schraufstatter, “Point mutation causing constitutive signaling of CXCR2 leads to transforming activity similar to Kaposi's sarcoma herpesvirus-G protein- coupled receptor,” Journal of Immunology, vol. 163, no. 4, pp. 2017–2022, 1999. View at Scopus
  102. M. M. Rosenkilde, T. N. Kledal, P. J. Holst, and T. W. Schwartz, “Selective elimination of high constitutive activity or chemokine binding in the human herpesvirus 8 encoded seven transmembrane oncogene ORF74,” Journal of Biological Chemistry, vol. 275, no. 34, pp. 26309–26315, 2000. View at Publisher · View at Google Scholar · View at Scopus
  103. M. N. Wakeling, D. J. Roy, A. A. Nash, and J. P. Stewart, “Characterization of the murine gammaherpesvirus 68 ORF74 product: a novel oncogenic G protein-coupled receptor,” Journal of General Virology, vol. 82, pp. 1187–1197, 2001. View at Scopus
  104. D. Verzijl, C. P. Fitzsimons, M. Van Dijk et al., “Differential activation of murine herpesvirus 68- and Kaposi's sarcoma-associated herpesvirus-encoded ORF74 G protein-coupled receptors by human and murine chemokines,” Journal of Virology, vol. 78, no. 7, pp. 3343–3351, 2004. View at Publisher · View at Google Scholar · View at Scopus
  105. Y. Isegawa, Z. Ping, K. Nakano, N. Sugimoto, and K. Yamanishi, “Human herpesvirus 6 open reading frame U12 encodes a functional β- chemokine receptor,” Journal of Virology, vol. 72, no. 7, pp. 6104–6112, 1998. View at Scopus
  106. C. P. Fitzsimons, U. A. Gompels, D. Verzijl et al., “Chemokine-directed trafficking of receptor stimulus to different G proteins: selective inducible and constitutive signaling by human herpesvirus 6-encoded chemokine receptor U51,” Molecular Pharmacology, vol. 69, no. 3, pp. 888–898, 2006. View at Publisher · View at Google Scholar · View at Scopus
  107. R. Case, E. Sharp, T. Benned-Jensen, M. M. Rosenkilde, N. Davis-Poynter, and H. E. Farrell, “Functional analysis of the murine cytomegalovirus chemokine receptor homologue M33: ablation of constitutive signaling is associated with an attenuated phenotype in vivo,” Journal of Virology, vol. 82, no. 4, pp. 1884–1898, 2008. View at Publisher · View at Google Scholar · View at Scopus
  108. Y. K. Gruijthuijsen, E. V. H. Beuken, M. J. Smit, R. Leurs, C. A. Bruggeman, and C. Vink, “Mutational analysis of the R33-encoded G protein-coupled receptor of rat cytomegalovirus: identification of amino acid residues critical for cellular localization and ligand-independent signalling,” Journal of General Virology, vol. 85, pp. 897–909, 2004. View at Publisher · View at Google Scholar · View at Scopus
  109. S. M. Rodems and D. H. Spector, “Extracellular signal-regulated kinase activity is sustained early during human cytomegalovirus infection,” Journal of Virology, vol. 72, no. 11, pp. 9173–9180, 1998. View at Scopus
  110. J. Vomaske, R. M. Melnychuk, P. P. Smith et al., “Differential ligand binding to a human cytomegalovirus chemokine receptor determines cell type-specific motility,” PLoS Pathogens, vol. 5, no. 2, Article ID e1000304, 2009. View at Publisher · View at Google Scholar · View at Scopus
  111. O. Pleskoff, P. Casarosa, L. Verneuil et al., “The human cytomegalovirus-encoded chemokine receptor US28 induces caspase-dependent apoptosis,” FEBS Journal, vol. 272, no. 16, pp. 4163–4177, 2005. View at Publisher · View at Google Scholar · View at Scopus
  112. D. Maussang, D. Verzijl, M. Van Walsum et al., “Human cytomegalovirus-encoded chemokine receptor US28 promotes tumorigenesis,” Proceedings of the National Academy of Sciences of the United States of America, vol. 103, no. 35, pp. 13068–13073, 2006. View at Publisher · View at Google Scholar · View at Scopus
  113. D. Maussang, E. Langemeijer, C. P. Fitzsimons et al., “The human cytomegalovirus-encoded chemokine receptor US28 promotes angiogenesis and tumor formation via cyclooxygenase-2,” Cancer Research, vol. 69, no. 7, pp. 2861–2869, 2009. View at Publisher · View at Google Scholar · View at Scopus
  114. E. Slinger, D. Maussang, A. Schreiber et al., “HCMV-encoded chemokine receptor US28 mediates proliferative signaling through the IL-6-STAT3 axis,” Science Signaling, vol. 3, no. 133, Article ID ra58, 2010. View at Publisher · View at Google Scholar · View at Scopus
  115. P. Ranganathan, P. A. Clark, J. S. Kuo, M. S. Salamat, and R. F. Kalejta, “Significant association of multiple human cytomegalovirus genomic loci with glioblastoma multiforme samples,” Journal of Virology, vol. 86, no. 2, pp. 854–864, 2012. View at Publisher · View at Google Scholar · View at Scopus
  116. K. G. Lucas, L. Bao, R. Bruggeman, K. Dunham, and C. Specht, “The detection of CMV pp65 and IE1 in glioblastoma multiforme,” Journal of Neuro-Oncology, vol. 103, no. 2, pp. 231–238, 2011. View at Publisher · View at Google Scholar · View at Scopus
  117. C. S. Cobbs, “Evolving evidence implicates cytomegalovirus as a promoter of malignant glioma pathogenesis,” Herpesviridae, vol. 2, no. 1, p. 10, 2011.
  118. K. Dziurzynski, J. Wei, W. Qiao et al., “Glioma-associated cytomegalovirus mediates subversion of the monocyte lineage to a tumor propagating phenotype,” Clinical Cancer Research, vol. 17, no. 14, pp. 4642–4649, 2011. View at Publisher · View at Google Scholar · View at Scopus
  119. R. Lyngaa, K. Nørregaard, M. Kristensen, V. Kubale, M. M. Rosenkilde, and T. N. Kledal, “Cell transformation mediated by the Epstein-Barr virus G protein-coupled receptor BILF1 is dependent on constitutive signaling,” Oncogene, vol. 29, no. 31, pp. 4388–4398, 2010. View at Publisher · View at Google Scholar · View at Scopus
  120. A. J. Butcher, R. Prihandoko, K. C. Kong et al., “Differential G-protein-coupled receptor phosphorylation provides evidence for a signaling bar code,” Journal of Biological Chemistry, vol. 286, no. 13, pp. 11506–11518, 2011. View at Publisher · View at Google Scholar · View at Scopus
  121. A. J. Butcher, K. C. Kong, R. Prihandoko, and A. B. Tobin, “Physiological role of g-protein coupled receptor phosphorylation,” Handbook of Experimental Pharmacology, vol. 208, pp. 79–94, 2012. View at Publisher · View at Google Scholar · View at Scopus
  122. S. K. Shenoy and R. J. Lefkowitz, “Multifaceted roles of β-arrestins in the regulation of seven-membrane-spanning receptor trafficking and signalling,” Biochemical Journal, vol. 375, pp. 503–515, 2003. View at Publisher · View at Google Scholar · View at Scopus
  123. S. K. Shenoy, P. H. McDonald, T. A. Kohout, and R. J. Lefkowitz, “Regulation of receptor fate by ubiquitination of activated β2-adrenergic receptor and β-arrestin,” Science, vol. 294, no. 5545, pp. 1307–1313, 2001. View at Publisher · View at Google Scholar · View at Scopus
  124. A. Fraile-Ramos, A. Pelchen-Matthews, T. N. Kledal, H. Browne, T. W. Schwartz, and M. Marsh, “Localization of HCMV UL33 and US27 in endocytic compartments and viral membranes,” Traffic, vol. 3, no. 3, pp. 218–232, 2002. View at Publisher · View at Google Scholar · View at Scopus
  125. E. A. Berger, “HIV entry and tropism: the chemokine receptor connection,” AIDS, vol. 11, pp. S3–16, 1997. View at Scopus
  126. A. Fraile-Ramos, T. N. Kledal, A. Pelchen-Matthews, K. Bowers, T. W. Schwartz, and M. Marsh, “The human cytomegalovirus US28 protein is located in endocytic vesicles and undergoes constitutive endocytosis and recycling,” Molecular Biology of the Cell, vol. 12, no. 6, pp. 1737–1749, 2001. View at Scopus
  127. A. Fraile-Ramos, T. A. Kohout, M. Waldhoer, and M. Marsh, “Endocytosis of the viral chemokine receptor US28 does not require beta-arrestins but is dependent on the clathrin-mediated pathway,” Traffic, vol. 4, no. 4, pp. 243–253, 2003. View at Scopus
  128. G. Alkhatib, C. Combadiere, C. C. Broder et al., “CC CKR5: a RANTES, MIP-1α, MIP-1β receptor as a fusion cofactor for macrophage-tropic HIV-1,” Science, vol. 272, no. 5270, pp. 1955–1958, 1996. View at Scopus
  129. Y. Feng, C. C. Broder, P. E. Kennedy, and E. A. Berger, “HIV-1 entry cofactor: functional cDNA cloning of a seven-transmembrane, G protein-coupled receptor,” Science, vol. 272, no. 5263, pp. 872–877, 1996. View at Scopus
  130. C.-Z. Dong, S. Tian, N. Madani et al., “Role of CXCR4 internalization in the anti-HIV activity of stromal cell-derived factor-1α probed by a novel synthetically and modularly modified-chemokine analog,” Experimental Biology and Medicine, vol. 236, no. 12, pp. 1413–1419, 2011. View at Publisher · View at Google Scholar · View at Scopus
  131. N. Signoret, J. Oldridge, A. Pelchen-Matthews et al., “Phorbol esters and SDF-1 induce rapid endocytosis and down modulation of the chemokine receptor CXCR4,” Journal of Cell Biology, vol. 139, no. 3, pp. 651–664, 1997. View at Publisher · View at Google Scholar · View at Scopus
  132. N. Signoret, M. M. Rosenkilde, P. J. Klasse et al., “Differential regulation of CXCR4 and CCR5 endocytosis,” Journal of Cell Science, vol. 111, pp. 2819–2830, 1998. View at Scopus
  133. P. J. Klasse, M. M. Rosenkilde, N. Signoret, A. Pelchen-Matthews, T. W. Schwartz, and M. Marsh, “CD4-chemokine receptor hybrids in human immunodeficiency virus type 1 infection,” Journal of Virology, vol. 73, no. 9, pp. 7453–7466, 1999. View at Scopus
  134. M. Oppermann, M. Mack, A. E. I. Proudfoot, and H. Olbrich, “Differential effects of CC chemokines on CC chemokine receptor 5 (CCR5) phosphorylation and identification of phosphorylation sites on the CCR5 carboxyl terminus,” Journal of Biological Chemistry, vol. 274, no. 13, pp. 8875–8885, 1999. View at Publisher · View at Google Scholar · View at Scopus
  135. I. Aramori, J. Zhang, S. S. G. Ferguson, P. D. Bieniasz, B. R. Cullen, and M. G. Caron, “Molecular mechanism of desensitization of the chemokine receptor CCR-5: receptor signaling and internalization are dissociable from its role as an HIV-1 co-receptor,” The EMBO Journal, vol. 16, no. 15, pp. 4606–4616, 1997. View at Publisher · View at Google Scholar · View at Scopus
  136. K. Kraft, H. Olbrich, I. Majoul, M. Mack, A. Proudfoot, and M. Oppermann, “Characterization of sequence determinants within the carboxyl-terminal domain of chemokine receptor CCR5 that regulate signaling and receptor internalization,” Journal of Biological Chemistry, vol. 276, no. 37, pp. 34408–34418, 2001. View at Publisher · View at Google Scholar · View at Scopus
  137. S. Venkatesan, A. Petrovic, M. Locati, Y. O. Kim, D. Weissman, and P. M. Murphy, “A membrane-proximal basic domain and cysteine cluster in the C-terminal tail of CCR5 constitute a bipartite motif critical for cell surface expression,” Journal of Biological Chemistry, vol. 276, no. 43, pp. 40133–40145, 2001. View at Publisher · View at Google Scholar · View at Scopus
  138. M. J. Orsini, J. L. Parent, S. J. Mundell, and J. L. Benovic, “Trafficking of the HIV coreceptor CXCR4. Role of arrestins and identification of residues in the C-terminal tail that mediate receptor internalization,” Journal of Biological Chemistry, vol. 274, no. 43, pp. 31076–31086, 1999. View at Publisher · View at Google Scholar · View at Scopus
  139. B. Haribabu, R. M. Richardson, I. Fisher et al., “Regulation of human chemokine receptors CXCR4: role of phosphorylation in desensitization and internalization,” Journal of Biological Chemistry, vol. 272, no. 45, pp. 28726–28731, 1997. View at Publisher · View at Google Scholar · View at Scopus
  140. T. Kawai, U. Choi, N. L. Whiting-Theobald et al., “Enhanced function with decreased internalization of carboxy-terminus truncated CXCR4 responsible for WHIM syndrome,” Experimental Hematology, vol. 33, no. 4, pp. 460–468, 2005. View at Publisher · View at Google Scholar · View at Scopus
  141. M. P. Stropes, O. D. Schneider, W. A. Zagorski, J. L. C. Miller, and W. E. Miller, “The carboxy-terminal tail of human cytomegalovirus (HCMV) US28 regulates both chemokine-independent and chemokine-dependent signaling in HCMV-infected cells,” Journal of Virology, vol. 83, no. 19, pp. 10016–10027, 2009. View at Publisher · View at Google Scholar · View at Scopus
  142. B. Bodaghi, T. R. Jones, D. Zipeto et al., “Chemokine sequestration by viral chemoreceptors as a novel viral escape strategy: withdrawal of chemokines from the environment of cytomegalovirus- infected cells,” Journal of Experimental Medicine, vol. 188, no. 5, pp. 855–866, 1998. View at Publisher · View at Google Scholar · View at Scopus
  143. T. Mokros, A. Rehm, J. Droese, M. Oppermann, M. Lipp, and U. E. Höpken, “Surface expression and endocytosis of the human cytomegalovirus-encoded chemokine receptor US28 is regulated by Agonist-independent phosphorylation,” Journal of Biological Chemistry, vol. 277, no. 47, pp. 45122–45128, 2002. View at Publisher · View at Google Scholar · View at Scopus
  144. M. Waldhoer, P. Casarosa, M. M. Rosenkilde et al., “The carboxyl terminus of human cytomegalovirus-encoded 7 transmembrane receptor US28 camouflages agonism by mediating constitutive endocytosis,” Journal of Biological Chemistry, vol. 278, no. 21, pp. 19473–19482, 2003. View at Publisher · View at Google Scholar · View at Scopus
  145. L. K. Stapleton, K. L. Arnolds, A. P. Lares, T. M. Devito, and J. V. Spencer, “Receptor chimeras demonstrate that the C-terminal domain of the human cytomegalovirus US27 gene product is necessary and sufficient for intracellular receptor localization,” Virology Journal, vol. 9, no. 1, article 42, 2012. View at Publisher · View at Google Scholar · View at Scopus
  146. C. Liu, G. Sandford, G. Fei, and J. Nicholas, “Galpha protein selectivity determinant specified by a viral chemokine receptor-conserved region in the C tail of the human herpesvirus 8 g protein-coupled receptor,” Journal of Virology, vol. 78, no. 5, pp. 2460–2471, 2004. View at Publisher · View at Google Scholar · View at Scopus
  147. M. Schwarz and P. M. Murphy, “Kaposi's sarcoma-associated herpesvirus G protein-coupled receptor constitutively activates NF-κB and induces proinflammatory cytokine and chemokine production via a C-terminal signaling determinant,” Journal of Immunology, vol. 167, no. 1, pp. 505–513, 2001. View at Scopus
  148. D. Verzijl, L. Pardo, M. Van Dijk et al., “Helix 8 of the viral chemokine receptor ORF74 directs chemokine binding,” Journal of Biological Chemistry, vol. 281, no. 46, pp. 35327–35335, 2006. View at Publisher · View at Google Scholar · View at Scopus
  149. J. Zuo, L. L. Quinn, J. Tamblyn et al., “The Epstein-Barr virus-encoded BILF1 protein modulates immune recognition of endogenously processed antigen by targeting major histocompatibility complex class I molecules trafficking on both the exocytic and endocytic pathways,” Journal of Virology, vol. 85, no. 4, pp. 1604–1614, 2011. View at Publisher · View at Google Scholar · View at Scopus