The highly conserved DRY motif of class A G protein-coupled receptors: Beyond the ground state

Molecular Pharmacology

Volumn 71, Issue 4, 2007, Pages 959-964

  Rovati, G Enrico ^a   Capra, Valérie ^a   Neubig, Richard R ^b  

^a UNIVERSITY OF MILAN   (Italy)

^b UNIVERSITY OF MICHIGAN MEDICAL SCHOOL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ARGININE; ASPARTIC ACID; G PROTEIN COUPLED RECEPTOR; GLUTAMIC ACID; RHODOPSIN; TYROSINE;

BINDING AFFINITY; CONFORMATIONAL TRANSITION; CRYSTAL STRUCTURE; PRIORITY JOURNAL; PROTEIN BINDING; PROTEIN STRUCTURE; SHORT SURVEY;

AMINO ACID MOTIFS; CONSERVED SEQUENCE; GTP-BINDING PROTEINS; MUTATION; PROTEIN CONFORMATION; RECEPTORS, G-PROTEIN-COUPLED;

EID: 33947381686     PISSN: 0026895X     EISSN: 15210111     Source Type: Journal    
DOI: 10.1124/mol.106.029470     Document Type: Short Survey

References (64)

1. Acharya S and Karnik SS (1996) Modulation of GDP release from transducin by the conserved Glu134-Arg135 sequence in rhodopsin. J Biol Chem 271:25406-25411.
2. 2 receptor. Mol Pharmacol 57:890-898.
3. Angelova K, Fanelli F, and Puett D (2002) A model for constitutive lutropin receptor activation based on molecular simulation and engineered mutations in transmembrane helices 6 and 7. J Biol Chem 277:32202-32213.
4. Arora KK, Cheng Z, and Catt KJ (1997) Mutations of the conserved DRS motif in the second intracellular loop of the gonadotropin-releasing hormone receptor affect expression, activation, and internalization. Mol Endocrinol 11:1203-1212.
5. Auger GA, Pease JE, Shen X, Xanthou G, and Barker MD (2002) Alanine scanning mutagenesis of CCR3 reveals that the three intracellular loops are essential for functional receptor expression. Eur J Immunol 32:1052-1058.
6. Ballesteros J, Kitanovic S, Guarnieri F, Davies P, Fromme BJ, Konvicka K, Chi L, Millar RP, Davidson JS, Weinstein H, et al. (1998) Functional microdomains in G-protein-coupled receptors. The conserved arginine-cage motif in the gonadotropin-releasing hormone receptor. J Biol Chem 273:10445-10453.
7. Ballesteros JA, Jensen AD, Liapakis G, Rasmussen SG, Shi L, Gether U, and Javitch JA (2001) Activation of the β2-adrenergic receptor involves disruption of an ionic lock between the cytoplasmic ends of transmembrane segments 3 and 6. J Biol Chem 276:29171-29177.
8. Barak LS, Oakley RH, Laporte SA, and Caron MG (2001) Constitutive arrestin-mediated desensitization of a human vasopressin receptor mutant associated with nephrogenic diabetes insipidus. Proc Natl Acad Sci USA 98:93-98.
9. Birnbaumer M (1995) Mutations and diseases of G protein coupled receptors. J Recept Signal Transduct Res 15:131-160.
10. Bockaert J and Pin JP (1999) Molecular tinkering of G protein-coupled receptors: an evolutionary success. EMBO (Eur Mol Biol Organ) J 18:1723-1729.
11. Bourne HR (1997) How receptors talk to trimeric G proteins. Curr Opin Cell Biol 9:134-142.
12. Brink CB, Harvey BH, Bodenstein J, Venter DP, and Oliver DW (2004) Recent advances in drug action and therapeutics: relevance of novel concepts in G-protein-coupled receptor and signal transduction pharmacology. Br J Clin Pharmacol 57:373-387.
13. Burstein ES, Spalding TA, and Brann MR (1998) The second intracellular loop of the m5 muscarinic receptor is the switch which enables G-protein coupling. J Biol Chem 273:24322-24327.
14. Capra V, Veltri A, Foglia C, Crimaldi L, Habib A, Parenti M, and Rovati GE (2004) Mutational analysis of the highly conserved ERY motif of the thromboxane A2 receptor: alternative role in G protein-coupled receptor signaling. Mol Pharmacol 66:880-889.
15. Chung DA, Wade SM, Fowler CB, Woods DD, Abada PB, Mosberg HI, and Neubig RR (2002) Mutagenesis and peptide analysis of the DRY motif in the alpha2A adrenergic receptor: evidence for alternate mechanisms in G protein-coupled receptors. Biochem Biophys Res Commun 293:1233-1241.
16. Cohen GB, Yang T, Robinson PR, and Oprian DD (1993) Constitutive activation of opsin: influence of charge at position 134 and size at position 296. Biochemistry 32:6111-6115.
17. Costa EM, Bedecarrats GY, Mendonca BB, Arnhold IJ, Kaiser UB, and Latronico AC (2001) Two novel mutations in the gonadotropin-releasing hormone receptor gene in Brazilian patients with hypogonadotropic hypogonadism and normal olfaction. J Clin Endocrinol Metab 86:2680-2686.
18. Cotecchia S, Bjorklof K, Rossier O, Stanasila L, Greasley P, and Fanelli F (2002) The alpha1b-adrenergic receptor subtype: molecular properties and physiological implications. J Recept Signal Transduct Res 22:1-16.
19. Dohlman HG, Thorner J, Caron MG, and Lefkowitz RJ (1991) Model systems for the study of seven-transmembrane-segment receptors. Annu Rev Biochem 60:653-688.
20. Drews J (2000) Drug discovery: a historical perspective. Science (Wash DC) 287:1960-1964.
21. Favre N, Fanelli F, Missotten M, Nichols A, Wilson J, di Tiani M, Rommel C, and Scheer A (2005) The DRY motif as a molecular switch of the human oxytocin receptor. Biochemistry 44:9990-10008.
22. Feng W and Song ZH (2003) Effects of D3.49A, R3.50A, and A6.34E mutations on ligand binding and activation of the cannabinoid-2 (CB2) receptor. Biochem Pharmacol 65:1077-1085.
23. Flanagan CA (2005) A GPCR that is not "DRY". Mol Pharmacol 68:1-3.
24. Franke RR, Sakmar TP, Graham RM, and Khorana HG (1992) Structure and function in rhodopsin. Studies of the interaction between the rhodopsin cytoplasmic domain and transducin. J Biol Chem 267:14767-14774.
25. Fredriksson R, Lagerstrom MC, Lundin LG, and Schioth HB (2003) The G-protein-coupled receptors in the human genome form five main families. Phylogenetic analysis, paralogon groups, and fingerprints. Mol Pharmacol 63:1256-1272.
26. Gaborik Z, Jagadeesh G, Zhang M, Spat A, Catt KJ, and Hunyady L (2003) The role of a conserved region of the second intracellular loop in AT1 angiotensin receptor activation and signaling. Endocrinology 144:2220-2228.
27. 2B-adrenoceptor. Biochem Biophys Res Commun 306:959-965.
28. 1b-adrenergic receptor highlight the role of the helix 3/helix 6 interface in receptor activation. Mol Pharmacol 61:1025-1032.
29. 1b-adrenergic receptor. Involvement of basic and hydrophobic residues in receptor activation and G protein coupling. J Biol Chem 276:46485-46494.
30. Hall RA, Premont RT, and Lefkowitz RJ (1999) Heptahelical receptor signaling: beyond the G protein paradigm. J Cell Biol 145:927-932.
31. Hawtin SR (2005) Charged residues of the conserved DRY triplet of the vasopressin V1a receptor provide molecular determinants for cell surface delivery and internalization. Mol Pharmacol 68:1172-1182.
32. Innamorati G, Sadeghi H, Eberle AN, and Birnbaumer M (1997) Phosphorylation of the V2 vasopressin receptor. J Biol Chem 272:2486-2492.
33. Janz JM and Farrens DL (2004) Rhodopsin activation exposes a key hydrophobic binding site for the transducin α-subunit C terminus. J Biol Chem 279:29767-29773.
34. Lagane B, Ballet S, Planchenault T, Balabanian K, Le Poul E, Blanpain C, Percherancier Y, Staropoli I, Vassart G, Oppermann M, et al. (2005) Mutation of the DRY motif reveals different structural requirements for the CC chemokine receptor 5-mediated signaling and receptor endocytosis. Mol Pharmacol 67:1966-1976.
35. Lefkowitz RJ (2000) The superfamily of heptahelical receptors. Nat Cell Biol 2:E133-E136.
36. Li J, Huang P, Chen C, de Riel JK, Weinstein H, and Liu-Chen LY (2001) Constitutive activation of the mu opioid receptor by mutation of D3.49(164), but not D3.32(147): D3.49(164) is critical for stabilization of the inactive form of the receptor and for its expression. Biochemistry 40:12039- 12050.
37. Lu ZL, Curtis CA, Jones PG, Pavia J, and Hulme EC (1997) The role of the aspartate-arginine-tyrosine triad in the m1 muscarinic receptor: mutations of aspartate 122 and tyrosine 124 decrease receptor expression but do not abolish signaling. Mol Pharmacol 51:234-241.
38. Marinissen MJ and Gutkind JS (2001) G-protein-coupled receptors and signaling networks: emerging paradigms. Trends Pharmacol Sci 22:368-376.
39. Maudsley S, Martin B, and Luttrell LM (2005) The origins of diversity and specificity in g protein-coupled receptor signaling. J Pharmacol Exp Ther 314:485-494.
40. Milligan G (2003) Principles: extending the utility of [35S]GTP gamma S binding assays. Trends Pharmacol Sci 24:87-90.
41. Morin D, Cotte N, Balestre MN, Mouillac B, Manning M, Breton C, and Barberis C (1998) The D136A mutation of the V2 vasopressin receptor induces a constitutive activity which permits discrimination between antagonists with partial agonist and inverse agonist activities. FEBS Lett 441:470-475.
42. Moro O, Lameh J, Hogger P, and Sadee W (1993) Hydrophobic amino acid in the i2 loop plays a key role in receptor-G protein coupling. J Biol Chem 268:22273-22276.
43. Ohyama K, Yamano Y, Sano T, Nakagomi Y, Wada M, and Inagami T (2002) Role of the conserved DRY motif on G protein activation of rat angiotensin II receptor type 1A. Biochem Biophys Res Commun 292:362-367.
44. Palczewski K, Kumasaka T, Hori T, Behnke CA, Motoshima H, Fox BA, Le Trong I, Teller DC, Okada T, Stenkamp RE, et al. (2000) Crystal structure of rhodopsin: A G protein-coupled receptor. Science (Wash DC) 289:739-745.
45. Pierce KL, Premont RT, and Lefkowitz RJ (2002) Seven-transmembrane receptors. Nat Rev Mol Cell Biol 3:639-650.
46. Rasmussen SG, Jensen AD, Liapakis G, Ghanouni P, Javitch JA, and Gether U (1999) Mutation of a highly conserved aspartic acid in the β2 adrenergic receptor: constitutive activation, structural instability, and conformational rearrangement of transmembrane segment 6. Mol Pharmacol 56:175-184.
47. Rhee MH, Nevo I, Levy R, and Vogel Z (2000) Role of the highly conserved Asp-Arg-Tyr motif in signal transduction of the CB2 cannabinoid receptor. FEBS Lett 466:300-304.
48. Rosenthal W, Antaramian A, Gilbert S, and Birnbaumer M (1993) Nephrogenic diabetes insipidus. A V2 vasopressin receptor unable to stimulate adenylyl cyclase. J Biol Chem 268:13030-13033.
49. Samama P, Cotecchia S, Costa T, and Lefkowitz RJ (1993) A mutation-induced activated state of the β2-adrenergic receptor. Extending the ternary complex model. J Biol Chem 268:4625-4636.
50. Scheer A, Fanelli F, Costa T, De Benedetti PG, and Cotecchia S (1996) Constitutively active mutants of the alpha 1B-adrenergic receptor: role of highly conserved polar amino acids in receptor activation. EMBO (Eur Mol Biol Organ) J 15:3566-3578.
51. Scheer A, Fanelli F, Costa T, De Benedetti PG, and Cotecchia S (1997) The activation process of the α1B-adrenergic receptor: potential role of protonation and hydrophobicity of a highly conserved aspartate. Proc Natl Acad Sci USA 94:808-813.
52. Schwartz TW (1994) Locating ligand-binding sites in 7TM receptors by protein engineering. Curr Opin Biotechnol 5:434-444.
53. Schwartz TW, Frimurer TM, Holst B, Rosenkilde MM, and Elling CE (2006) Molecular mechanism of 7tm receptor activation-a global toggle switch model. Annu Rev Pharmacol Toxicol 46:481-519.
54. Shapiro DA, Kristiansen K, Weiner DM, Kroeze WK, and Roth BL (2002) Evidence for a model of agonist-induced activation of 5-hydroxytryptamine 2A serotonin receptors that involves the disruption of a strong ionic interaction between helices 3 and 6. J Biol Chem 277:11441-11449.
55. Shibata T, Suzuki C, Ohnishi J, Murakami K, and Miyazaki H (1996) Identification of regions in the human angiotensin II receptor type 1 responsible for Gi and Gq coupling by mutagenesis study. Biochem Biophys Res Commun 218:383-389.
56. Strader CD, Fong TM, Tota MR, Underwood D, and Dixon RA (1994) Structure and function of G protein-coupled receptors. Annu Rev Biochem 63:101-132.
57. Teller DC, Okada T, Behnke CA, Palczewski K, and Stenkamp RE (2001) Advances in determination of a high-resolution three-dimensional structure of rhodopsin, a model of G-protein-coupled receptors (GPCRs). Biochemistry 40:7761-7772.
58. Wang CD, Buck MA, and Fraser CM (1991) Site-directed mutagenesis of alpha 2A-adrenergic receptors: identification of amino acids involved in ligand binding and receptor activation by agonists. Mol Pharmacol 40:168-179.
59. Wei H, Ahn S, Shenoy SK, Karnik SS, Hunyady L, Luttrell LM, and Lefkowitz RJ (2003) Independent β-arrestin 2 and G protein-mediated pathways for angiotensin II activation of extracellular signal-regulated kinases 1 and 2. Proc Natl Acad Sci USA 100:10782-10787.
60. Wess J (1998) Molecular basis of receptor/G-protein-coupling selectivity. Pharmacol Ther 80:231-264.
61. Wilbanks AM, Laporte SA, Bohn LM, Barak LS, and Caron MG (2002) Apparent loss-of-function mutant GPCRs revealed as constitutively desensitized receptors. Biochemistry 41:11981-11989.
62. Wise A, Jupe SC, and Rees S (2004) The identification of ligands at orphan G-protein coupled receptors. Annu Rev Pharmacol Toxicol 44:43-66.
63. Zhang M, Mizrachi D, Fanelli F, and Segaloff DL (2005) The formation of a salt bridge between helices 3 and 6 is responsible for the constitutive activity and lack of hormone responsiveness of the naturally occurring L457R mutation of the human lutropin receptor. J Biol Chem 280:26169- 26176.
64. Zhu SZ, Wang SZ, Hu J, and el-Fakahany EE (1994) An arginine residue conserved in most G protein-coupled receptors is essential for the function of the m1 muscarinic receptor. Mol Pharmacol 45:517-523.