GPCR structure and activation: An essential role for the first extracellular loop in activating the adenosine A2B receptor

FASEB Journal

Volumn 25, Issue 2, 2011, Pages 632-643

  Peeters, Miriam C ^a   Van Westen, Gerard J P ^a   Guo, Dong ^a   Wisse, Lisanne E ^a   Müller, Christa E ^b   Beukers, Margot W ^a   Ijzerman, Adriaan P ^a  

^a LEIDEN UNIVERSITY   (Netherlands)

^b UNIVERSITY OF BONN   (Germany)

Author keywords

Constitutive activity; G protein coupled receptors; Mutagenesis; Receptor activation; S. cerevisiae

Indexed keywords

4 [2 [7 AMINO 2 (2 FURYL) 1,2,4 TRIAZOLO[2,3 A][1,3,5]TRIAZIN 5 YLAMINO]ETHYL]PHENOL; ADENOSINE 5' (N ETHYLCARBOXAMIDE); ADENOSINE A2A RECEPTOR; ADENOSINE A2B RECEPTOR; ASPARTIC ACID; PHENYLALANINE;

ARTICLE; CONTROLLED STUDY; EXTRACELLULAR LOOP; EXTRACELLULAR SPACE; GENE MUTATION; LIGAND BINDING; MUTAGENESIS; NONHUMAN; PRIORITY JOURNAL; PROTEIN DOMAIN; PROTEIN STRUCTURE; PROTEIN TERTIARY STRUCTURE; SACCHAROMYCES CEREVISIAE; SITE DIRECTED MUTAGENESIS; SITE SATURATION MUTAGENESISS;

ADENOSINE A2 RECEPTOR AGONISTS; ADENOSINE A2 RECEPTOR ANTAGONISTS; ADENOSINE-5'-(N-ETHYLCARBOXAMIDE); AMINO ACID SEQUENCE; AMINOPYRIDINES; GENE EXPRESSION REGULATION; HUMANS; MODELS, MOLECULAR; MOLECULAR STRUCTURE; MUTAGENESIS, SITE-DIRECTED; PROTEIN CONFORMATION; RECEPTOR, ADENOSINE A2B; SACCHAROMYCES CEREVISIAE; TRIAZINES; TRIAZOLES;

SACCHAROMYCES CEREVISIAE;

EID: 79551650974     PISSN: 08926638     EISSN: 15306860     Source Type: Journal    
DOI: 10.1096/fj.10-164319     Document Type: Article

References (48)

1. Olah, M. E., Jacobson, K. A., and Stiles, G. L. (1994) Role of the second extracellular loop of adenosine receptors in agonist and antagonist binding. Analysis of chimeric A1/A3 adenosine receptors. J. Biol. Chem. 269, 24692-24698
2. Klco, J., Wiegand, C., Narzinski, K., and Baranski, T. (2005) Essential role for the second extracellular loop in C5a receptor activation. Nat. Struct. Mol. Biol. 12, 320-326
3. Massotte, D., and Kieffer, B. L. (2005) The second extracellular loop: a damper for G protein-coupled receptors? Nat. Struct. Mol. Biol. 12, 287-288
4. Jaakola, V. P., Griffith, M. T., Hanson, M. A., Cherezov, V., Chien, E. Y., Lane, J. R., IJzerman, A. P., and Stevens, R. C. (2008) The 2.6 angstrom crystal structure of a human A2A adenosine receptor bound to an antagonist. Science 322, 1211-1217
5. Klco, J., Nikiforovich, G., and Baranski, T. (2006) Genetic analysis of the first and third extracellular loops of the C5a receptor reveals an essential WXFG motif in the first loop. J. Biol. Chem. 281, 12010-12019
6. Vassart, G., Pardo, L., and Costagliola, S. (2004) A molecular dissection of the glycoprotein hormone receptors. Trends Biochem. Sci. 29, 119-126
7. Nurwakagari, P., Breit, A., Hess, C., Salman-Livny, H., Ben-Menahem, D., and Gudermann, T. (2007) A conformational contribution of the luteinizing hormone-receptor ectodomain to receptor activation. J. Mol. Endocrinol. 38, 259-275
8. Kleinau, G., Jaeschke, H., Mueller, S., Raaka, B. M., Neumann, S., Paschke, R., and Krause, G. (2008) Evidence for cooperative signal triggering at the extracellular loops of the TSH receptor. FASEB J. 22, 2798-2808
9. Sura-Trueba, S., Aumas, C., Carre, A., Durif, S., Leger, J., Polak, M., and de Roux, N. (2009) An inactivating mutation within the first extracellular loop of the thyrotropin receptor impedes normal posttranslational maturation of the extracellular domain. Endocrinology 150, 1043-1050
10. Mizutori, Y., Chen, C. R., McLachlan, S. M., and Rapoport, B. (2008) The thyrotropin receptor hinge region is not simply a scaffold for the leucine-rich domain but contributes to ligand binding and signal transduction. Mol. Endocrinol. 22, 1171-1182
11. Fredholm, B. B., Arslan, G., Halldner, L., Kull, B., Schulte, G., and Wasserman, W. (2000) Structure and function of adenosine receptors and their genes. Naunyn Schmiedebergs Arch. Pharmacol. 362, 364-374
12. Fredholm, B. B., IJzerman, A. P., Jacobson, K. A., Klotz, K. N., and Linden, J. (2001) International Union of Pharmacology. XXV. Nomenclature and classification of adenosine receptors. Pharmacol. Rev. 53, 527-552
13. Wilson, C. N. (2008) Adenosine receptors and asthma in humans. Br. J. Pharmacol. 155, 475-486
14. Spicuzza, L., Di Maria, G., and Polosa, R. (2006) Adenosine in the airways: implications and applications. Eur. J. Pharmacol. 533, 77-88
15. Hasko, G., Linden, J., Cronstein, B., and Pacher, P. (2008) Adenosine receptors: therapeutic aspects for inflammatory and immune diseases. Nat. Rev. Drug Discov. 7, 759-770
16. Brown, A., Dyos, S., Whiteway, M., White, J., Watson, M., Marzioch, M., Clare, J., Cousens, D., Paddon, C., Plumpton, C., Romanos, M., and Dowell, S. (2000) Functional coupling of mammalian receptors to the yeast mating pathway using novel yeast/mammalian G protein alpha-subunit chimeras. Yeast 16, 11-22
17. Stewart, G. D., Valant, C., Dowell, S. J., Mijaljica, D., Devenish, R. J., Scammells, P. J., Sexton, P. M., and Christopoulos, A. (2009) Determination of adenosine A1 receptor agonist and antagonist pharmacology using Saccharomyces cerevisiae: implications for ligand screening and functional selectivity. J. Pharmacol. Exp. Ther. 331, 277-286
18. Beukers, M., van Oppenraaij, J., van der Hoorn, P., Blad, C., den Dulk, H., Brouwer, J., and IJzerman, A. (2004) Random mutagenesis of the human adenosine A2B receptor followed by growth selection in yeast. Identification of constitutively active and gain of function mutations. Mol. Pharmacol. 65, 702-710
19. Beukers, M., and IJzerman, A. (2005) Techniques: how to boost GPCR mutagenesis studies using yeast. Trends Pharmacol. Sci. 26, 533-539
20. Fromant, M., Blanquet, S., and Plateau, P. (1995) Direct random mutagenesis of gene-sized DNA fragments using polymerase chain reaction. Anal. Biochem. 224, 347-353
21. Olesnicky, N. S., Brown, A. J., Dowell, S. J., and Casselton, L. A. (1999) A constitutively active G-protein-coupled receptor causes mating self-compatibility in the mushroom Coprinus. EMBO J. 18, 2756-2763
22. Li, Q., Ye, K., Blad, C. C., den Dulk, H., Brouwer, J., IJzerman, A. P., and Beukers, M. W. (2007) ZM241385, DPCPX, MRS1706 are inverse agonists with different relative intrinsic efficacies on constitutively active mutants of the human adenosine A2B receptor. J. Pharmacol. Exp. Ther. 320, 637-645
23. Eckle, T., Krahn, T., Grenz, A., Kohler, D., Mittelbronn, M., Ledent, C., Jacobson, M. A., Osswald, H., Thompson, L. F., Unertl, K., and Eltzschig, H. K. (2007) Cardioprotection by ecto-5′-nucleotidase (CD73) and A2B adenosine receptors. Circulation 115, 1581-1590
24. Borrmann, T., Hinz, S., Bertarelli, D. C., Li, W., Florin, N. C., Scheiff, A. B., and Muller, C. E. (2009) 1-alkyl-8-(piperazine-1-sulfonyl) phenylxanthines: development and characterization of adenosine A2B receptor antagonists and a new radioligand with subnanomolar affinity and subtype specificity. J. Med. Chem. 52, 3994-4006
25. Chemical Computing Group, Inc. (2008) Molecular Operating Environment 2008.10, Chemical Computing Group, Quebec, QC, Canada
26. Wang, J., Cieplak, P., and Kollman, P. (2000) How well does a restrained electrostatic potential (RESP) model perform in calculating conformational energies of organic and biological molecules? J. Comput. Chem. 21, 1049-1074
27. Härterich, S., Koschatzky, S., Einsiedel, J., and Gmeiner, P. (2008) Novel insights into GPCR-peptide interactions: mutations in extracellular loop 1, ligand backbone methylations and molecular modeling of neurotensin receptor 1. Bioorg. Med. Chem. 16, 9359-9368
28. Bajaj, A., Connelly, S. M., Gehret, A. U., Naider, F., and Dumont, M. E. (2007) Role of extracellular charged amino acids in the yeast alpha-factor receptor. Biochim. Biophys. Acta 1773, 707-717
29. Langer, I., Vertongen, P., Perret, J., Waelbroeck, M., and Robberecht, P. (2003) Lysine 195 and aspartate 196 in the first extracellular loop of the VPAC1 receptor are essential for high affinity binding of agonists but not of antagonists. Neuropharmacology 44, 125-131
30. Hauser, M., Kauffman, S., Lee, B. K., Naider, F., and Becker, J. M. (2007) The first extracellular loop of the Saccharomyces cerevisiae GPCR STE2P undergoes a conformational change upon ligand binding. J. Biol. Chem.
31. Hawtin, S., Simms, J., Conner, M., Lawson, Z., Parslow, R., Trim, J., Sheppard, A., and Wheatley, M. (2006) Charged extracellular residues, conserved throughout a G-protein-coupled receptor family, are required for ligand binding, receptor activation, and cell-surface expression. J. Biol. Chem. 281, 38478-38488
32. Ballesteros, J. A., and Weinstein, H. (1995) Integrated methods for the construction of three dimensional models and computational probing of structure - function relations in G-protein coupled receptors. Methods Neurosci. 25, 366-428
33. Labrou, N. E., Bhogal, N., Hurrell, C. R., and Findlay, J. B. (2001) Interaction of Met297 in the seventh transmembrane segment of the tachykinin NK2 receptor with neurokinin A. J. Biol. Chem. 276, 37944-37949
34. Hjorth, S. A., Schambye, H. T., Greenlee, W. J., and Schwartz, T. W. (1994) Identification of peptide binding residues in the extracellular domains of the AT1 receptor. J. Biol. Chem. 269, 30953-30959
35. Fishman, G. A., Stone, E. M., Gilbert, L. D., and Sheffield, V. C. (1992) Ocular findings associated with a rhodopsin gene codon 106 mutation. Glycine-to-arginine change in autosomal dominant retinitis pigmentosa. Arch. Ophthalmol. 110, 646-653
36. Vaithinathan, R., Berson, E. L., and Dryja, T. P. (1994) Further screening of the rhodopsin gene in patients with autosomal dominant retinitis pigmentosa. Genomics 21, 461-463
37. Pasel, K., Schulz, A., Timmermann, K., Linnemann, K., Hoeltzenbein, M., Jaaskelainen, J., Gruters, A., Filler, G., and Schoneberg, T. (2000) Functional characterization of the molecular defects causing nephrogenic diabetes insipidus in eight families. J. Clin. Endocrinol. Metab. 85, 1703-1710
38. Tenenbaum-Rakover, Y., Commenges-Ducos, M., Iovane, A., Aumas, C., Admoni, O., and de Roux, N. (2007) Neuroendocrine phenotype analysis in five patients with isolated hypogonadotropic hypogonadism due to a L102P inactivating mutation of GPR54. J. Clin. Endocrinol. Metab. 92, 1137-1144
39. Parma, J., Van Sande, J., Swillens, S., Tonacchera, M., Dumont, J., and Vassart, G. (1995) Somatic mutations causing constitutive activity of the thyrotropin receptor are the major cause of hyperfunctioning thyroid adenomas: identification of additional mutations activating both the cyclic adenosine 3′,5′-monophosphate and inositol phosphate-Ca2+ cascades. Mol. Endocrinol. 9, 725-733
40. Noda, K., Saad, Y., Graham, R. M., and Karnik, S. S. (1994) The high affinity state of the beta 2-adrenergic receptor requires unique interaction between conserved and nonconserved extracellular loop cysteines. J. Biol. Chem. 269, 6743-6752
41. Dohlman, H. G., Caron, M. G., DeBlasi, A., Frielle, T., and Lefkowitz, R. J. (1990) Role of extracellular disulfide-bonded cysteines in the ligand binding function of the beta 2-adrenergic receptor. Biochemistry 29, 2335-2342
42. Moro, S., Hoffmann, C., and Jacobson, K. (1999) Role of the extracellular loops of G protein-coupled receptors in ligand recognition: a molecular modeling study of the human P2Y1 receptor. Biochemistry 38, 3498-3507
43. Branden, C., and Tooze, J. (1991) Introduction to Protein Structure, Garland, New York and London
44. Archer-Lahlou, E., Tikhonova, I., Escrieut, C., Dufresne, M., Seva, C., Pradayrol, L., Moroder, L., Maigret, B., and Fourmy, D. (2005) Modeled structure of a G-protein-coupled receptor: the cholecystokinin-1 receptor. J. Med. Chem. 48, 180-191
45. Genoud, S., Kajumo, F., Guo, Y., Thompson, D., and Dragic, T. (1999) CCR5-Mediated human immunodeficiency virus entry depends on an amino-terminal gp120-binding site and on the conformational integrity of all four extracellular domains. J. Virol. 73, 1645-1648
46. Langer, I., Tikhonova, I. G., Travers, M. A., Archer-Lahlou, E., Escrieut, C., Maigret, B., and Fourmy, D. (2005) Evidence that interspecies polymorphism in the human and rat cholecystokinin receptor-2 affects structure of the binding site for the endogenous agonist cholecystokinin. J. Biol. Chem. 280, 22198-22204
47. Cain, S. A., Woodruff, T. M., Taylor, S. M., Fairlie, D. P., Sanderson, S. D., and Monk, P. N. (2001) Modulation of ligand selectivity by mutation of the first extracellular loop of the human C5a receptor. Biochem. Pharmacol. 61, 1571-1579
48. Sung, C. H., Schneider, B. G., Agarwal, N., Papermaster, D. S., and Nathans, J. (1991) Functional heterogeneity of mutant rhodopsins responsible for autosomal dominant retinitis pigmentosa. Proc. Natl. Acad. Sci. U. S. A. 88, 8840-8844