Molecular mechanisms of GPCR activation

Ligand Design for G Protein-coupled Receptors

Volumn 30, Issue , 2006, Pages 83-97

  Bywater, Robert P ^a   Denny Gouldson, P ^b  

^a ADELARD LLP   (United Kingdom)

^b 14 TM Ltd   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

MOLECULAR MECHANISM;

MOLECULAR INTERACTIONS;

EID: 84879208493     PISSN: None     EISSN: None     Source Type: Book    
DOI: 10.1002/3527608249.ch5     Document Type: Chapter

References (100)

1. Hayward S, Berendsen HJC. Systematic analysis of domain motions in proteins from conformational change. Proteins, Struct, Funct Genet 1998; 30: 144-154.
2. See also http://www.cmp.uea. ac.uk/dyndom 2 Teller DC, Okada T, Behnke CA, Palczewski K, Stenkamp RE. Advances in determination of a high-resolution three-dimensional structure of rhodopsin, a model of G-protein-coupled receptors (GPCRs). Biochemistry 2001; 40: 7761-7772.
3. Teller DC, Okada T, Stenkamp RE, Yamamoto M, Miyano M. Crystal structure of rhodopsin: A G protein-coupled receptor. Science 2000; 289. 739-745.
4. Palczewski K, Kumasaka T, Hori T, Behnke CA, Motoshima H, Fox BA, Le Trong I,Teller DC, Okada T, Stenkamp RE,Yamamoto M, MiyanoM. Crystal structure of rhodopsin: A G protein-coupled receptor. Science 2000; 289: 739-745.
5. Li J, Edwards PC, Burghammer M, Villa, C, Schertler, G.F. Structure of bovine rhodopsin in a trigonal crystal form. J Mol Biol 2004; 343: 1409-1438.
6. Ruprecht JJ, Mielke T,Vogel R, Villa C, Schertler GFX. Electron crystallography reveals the structure of metarhodopsin I. EMBO J 2004; 23: 3609-3620.
7. Gouldson PR, Kidley NJ, Bywater RP, Psaroudakis G, Brooks HD, Diaz C, Shire D, Reynolds CA. Toward the active conformations of rhodopsin and the beta2-adrenergic receptor. Proteins, Struct, Funct Genet 2004; 56: 67-84.
8. Leff P. The two-state model of receptor activation. TIPS 1995; 16: 89-97.
9. Bywater RP. Location and nature of the residues important for ligand recognition in G-protein coupled receptors. J Mol Recognit 2005; 18: 60-72.
10. Sheikh SP,Vilardarga JP, Baranski TJ, Lichtarge, O, Iiri T, Meng EC, Nissenson RA, Bourne HR. Similar structures and shared switch mechanisms of the beta-2-adrenoceptor and the parathyroid hormone receptor. Zn(II) bridges between helices III and VI block activation. J Biol Chem 1999; 274: 17033-17041.
11. Strader CD, Fong TM,Tota MR, Underwood D, Dixon RAF. Structure and function of G protein-coupled receptors. Ann Rev Biochem 1994; 63: 101-132.
12. Gouldson P, Calandra B, Legoux P, Kerneis A, Rinaldi-Carmona M, Barth F, Le Fur G, Ferrara P, Shire D. Mutational analysis and molecular modelling of the antagonist SR 144528 binding site on the human cannabinoid CB(2) receptor. Eur J Pharmacol 2000; 401: 17-25.
13. Wieland K, Laak AM, Smit MJ, Kuhne R,Timmerman H, Leurs R. Mutational analysis of the antagonist binding site of the histamine H(1) receptor. J Biol Chem 1999; 274, 29994-30000.
14. Javitch JA, Shi L, Simpson MM, Chen J, Chiappa V,Visiers I, Weinstein H, Ballesteros JA. The fourth transmembrane segment of the dopamine D2 receptor: accessibility in the binding-site crevice and position in the transmembrane bundle. Biochemistry 2000; 39: 12190-12199.
15. Suryanarayana S, von Zastrow M, Kobilka BK. Identification of intramolecular interactions in adrenergic receptors. J Biol Chem 1992; 267: 21991-21994.
16. Soudijn W,Van Wijngaarden I, Ijzerman AP. Allosteric modulators of G-protein coupled receptors: perspectives and recent developments. Drug Discovery Today 2004; 9: 752-758.
17. May LT, Avlani VA, Sexton PM, Christopoulos A. Allosteric modulation of G protein-coupled receptors. Curr Pharm Des 2004; 10: 2003-2013.
18. Christopoulos A, Kenakin T. G-protein coupled receptors: allosterism and complexing. Pharm Rev 2002; 54: 323-374.
19. Birdsall NJ, Lazareno S, Popham A, Saldanha J. Multiple allosteric sites on muscarinic receptors. Life Sci 2001; 68: 2517-2524.
20. Järv J. A model of non-exclusive binding of agonist and antagonist on G-protein coupled receptors. J Theoret Biol 1995; 175: 577-582.
21. Seeley RJ, Drazen DL, Clegg DJ. The critical role of the melanocortin system in the control of energy balance. Annu Rev Nutr 2004; 24. 133-149.
22. Haskell-Luevano C, Nikiforovich G, Sharma SD,Yang YK, Dickinson C, Hruby VJ, Gantz I. Biological and conformational examination of stereochemical modifications using the template melanotropin peptide, Ac-Nle-c[Asp-His-Phe-Arg-Trp-Ala-Lys]-NH2, on human melanocortin receptors. JMed Chem 1997; 40: 1738-1748.
23. Pritchard LE, Armstrong D, Davies N, Oliver RL, Schmitz CA, Brennand JC,Wilkinson GF,White A. Agouti-related protein (83-132) is a competitive antagonist at the human melanocortin-4 receptor. J Endocrinol 2004; 180: 183-191.
24. Haskell-Luevano C, Lim S,Yuan W, Cone RD, Hruby VJ. Structure activity studies of the melanocortin antagonist SHU9119 modified at the 6, 7, 8, and 9 positions. Peptides 2000; 21: 49-57.
25. Radu CG, Nijagal A, McLaughlin J, Wang L,Witte ON. Differential proton sensitivity of related G protein-coupled receptors T cell death-associated gene 8 and G2A expressed in immune cells. Proc Natl Acad Sci USA 2005; 102: 1632-1637.
26. Ludwig MG,Vanek M, Guerini D, Gasser JA, Jones CE, Junker U, Hofstetter H,Wolf RM, Seuwen K. Proton-sensing G-protein-coupled receptors. Nature 2003; 425: 93-98.
27. Ishii S, Kihara Y, Shimizu T. Identification of T Cell Death-associated Gene 8 (TDAG8) as a Novel Acid Sensing G-protein-coupled Receptor. J Biol Chem 2005; 280: 9083-9087.
28. Sin WC, Zhang Y, Zhong W, Adhikarakunnathu S, Powers S, Hoey T, An S,Yang J. G protein-coupled receptors GPR4 and TDAG8 are oncogenic and overexpressed in human cancers. Oncogene 2004; 23: 6299-6303.
29. Kostenis E. Novel clusters of receptors for sphingosine-1-phosphate, sphingosylphosphorylcholine, and (lyso)-phosphatidic acid: new receptors for "old" ligands. J Cell Biochem 2004; 92: 923-936.
30. Bektas M, Barak LS, Jolly PS, Liu H, Lynch KR, Lacana E, Suhr KB, Milstien S, Spiegel S. The G proteincoupled receptor GPR4 suppresses ERK activation in a ligand-independent manner. Biochemistry 2003; 42: 12181-12191.
31. Wang JQ, Kon J, Mogi C,Tobo M, Damirin A, Sato K, Komachi M, Malchinkhuu E, Murata N, Kimura T, Kuwabara A,Wakamatsu K, Koizumi H, Uede T,Tsujimoto G, Kurose H, Sato T, Harada A, Misawa N,Tomura H, Okajima F. TDAG8 is a proton-sensing and psychosine-sensitive G-proteincoupled receptor. J Biol Chem 2004; 279: 45626-45633.
32. Murakami N,Yokomizo T, Okuno T, Shimizu T. G2A is a proton-sensing G-protein-coupled receptor antagonized by lysophosphatidylcholine. J Biol Chem 2004; 279: 42484-42491.
33. Dupre, D.J, Rola-Pleszczynski, M, Stankova, J. Inverse agonism: more than reverting constitutively active receptor signaling. Biochem Cell Biol 2004; 82: 676-680.
34. Kenakin T. Efficacy as a vector: the relative prevalence and paucity of inverse agonism. Mol Pharmacol 2004; 65: 2-11.
35. Strange PG. Mechanisms of inverse agonism at G-protein-coupled receptors. Trends Pharmacol Sci 2002; 23: 89-95.
36. De Ligt, R.A, Kourounakis, A.P, IJzerman, A.P. Inverse agonism at G protein-coupled receptors: (patho)physiological relevance and implications for drug discovery. Br J Pharmacol 2000; 130: 1-12.
37. Milligan G, Bond RA. Inverse agonism and the regulation of receptor number. Trends Pharmacol Sci 1997; 18: 468-474.
38. Chidiac P, Hebert TE,Valiquette M, Dennis, M, Bouvier M. Inverse agonist activity of beta-adrenergic antagonists. Mol Pharmacol 1994; 45: 490-499.
39. Seifert R,Wenzel-Seifert K. Constitutive activity of G-protein-coupled receptors:cause of disease and common property of wild-type receptors. Naunyn Schmiedebergs Arch Pharmacol 2002; 366: 381-416.
40. Parnot C, Miserey-Lenkei, S, Bardin, S, Corvol, P, Clauser, E. Lessons from constitutively active mutants of G-protein coupled receptors. Trends Endocrinol Metabol 2002; 13: 336-343.
41. Kim JM, Altenbach C, Kono M, Oprian DD,Hubbell WL, Khorana HG. Structural origins of constitutive activation in rhodopsin: Role of the K296/E113 salt bridge. Proc Natl Acad Sci USA 2004; 101: 12508-12513.
42. Ghanouni P, Steenhuis JJ, Farrens DL, Kobilka BK. Agonist-induced conformational changes in the G-protein-coupling domain of the beta-2-adrenergic receptor. Proc Natl Acad Sci USA 2001; 98: 5997-6002.
43. Ballesteros JA, Jensen AD, Liapakis G, Rasmussen SG, Shi L, Gether U, Javitch JA. Activation of the beta-2-adrenergic receptor involves disruption of an ionic lock between the cytoplasmic ends of transmembrane segments 3 and 6. J Biol Chem 2001; 276: 29171-29177.
44. Rasmussen SGF, Jensen AD, Lapiakis G, Ghanouni P, Javitch JA, Gether U. Mutation of a highly conserved aspartic acid in the α2 adrenergic receptor: constitutive activation, structural instability and conformational rearrangement of transmembrane segment 6. Mol Pharmacol 1999; 56: 175-184.
45. Altenbach C,Yang K, Farrens DL, Farahbakhsh ZT, Khorana HG, Hubbell WL. Structural features and light-dependent changes in the cytoplasmic interhelical e-f loop region of rhodopsin -a site-directed spin-labeling study. Biochemistry 1996; 35: 12470-12478.
46. Altenbach, C, Cai K, Khorana HG, Hubbell WL. Structural features and light-dependent changes in the sequence 306-322 extending from helix VII to the palmitoylation sites in rhodopsin: a sitedirected spin-labeling study. Biochemistry 1999; 38: 7931-7937.
47. Gether and Kobilka, G protein-coupled receptors. II Mechanism of against activation. J Biol Chem 1998; 273: 17979-17982.
48. Spalding TA, Burstein ES, Henderson SC, Ducote KR, Brann MR. Identification of a liganddependent switch within a muscarinic receptor. J Biol Chem 1998; 273: 21563-21568.
49. Altenbach C, Klein-Seetharaman J, Hwa J, Khorana HG, Hubbell WL. Structural features and light-dependent changes in the sequence 59-75 connecting helices I and II in rhodopsin: a sitedirected spin-labeling study. Biochemistry 1999; 38: 7945-7949.
50. HanM, Smith SO, Sakmar TP. Constitutive activation of opsin by mutation of methionine 257 on transmembrane helix 6. Biochemistry 1998; 37: 8253-8261.
51. Sommers CM, Martin NP, Akal-Strader A, Becker JM, Naider F, Dumont M. A limited spectrum of mutants causes constitutive activation of the yeast alpha-factor receptor. Biochemistry 2000; 39: 6898-6909.
52. Chen S, Lin F, Xu M, Graham RM. Phe303 in TM6 of the alpha1Badrenergic receptor is a key residue coupling TM helical movements to G-protein activation. Biochemistry 2002; 41: 588-596.
53. Befort K, Zilliox C, Filliol D,Yue SY, Kieffer BL. Constitutive activation of the mu-opioid receptor by mutations in transmembrane domains III and VII J Biol Chem 1999; 274: 18574-18581.
54. Wissink S,Van der Burg B, Katzenellenbogen B.S,Van der Saag PT. Synergistic activation of the serotonin-1A receptor by nuclear factor-kappa B and estrogen. Mol Endocrinol 2001; 15: 543-552.
55. Lagane B, Gaibelet G, Meilhoc E, Masson J-M, Cézanne L, Lopez A. Role of sterols in modulating the human ?-opioid receptor function in Saccharomyces cerevisiae. Biol Chem 2000; 43: 33197-33200.
56. Bissantz C, Bernard P, Hibert M, Rognan D. Protein-based virtual screening of chemical databases. II. Are homology models of G-protein coupled receptors suitable targets? Proteins, Struct, Funct Genet 2003; 50: 5-25.
57. Javitch JA, Fu DY, Liapakis G, Chen JY. Constitutive activation of the beta(2) Adrenergic receptor alters the orientation of its sixth membrane-spanning segment. J Biol Chem 1997; 272: 18546-18549.
58. Kono M,Yu H, Oprian DD. Disulfide bond exchange in rhodopsin. Biochemistry 1998; 37: 1302-1305.
59. Yu H, Kono M, Oprian DD. Statedependent disulfide cross-linking in rhodopsin. Biochemistry 1999; 38: 12028-12032.
60. Huang P,Visiers I,Weinstein H, Liu-Chen LY. The local environment at the cytoplasmic end of TM6 of the mu-opioid receptor differs from those of rhodopsin and monoamine receptors:introduction of an ionic lock between the cytoplasmic ends of helices 3 and 6 by a L6.30(275)E mutation inactivates the mu-opioid receptor and reduces the constitutive activity of its T6.34(279)K mutant. Biochemistry 2002; 41: 11972-11980.
61. Sansom MS,Weinstein H. Hinges, swivels and switches: the role of prolines in signalling via transmembrane alphahelices. Trends Pharmacol Sci 2000; 21: 445-451.
62. Prioleau C,Visiers I, Ebersole BJ, Weinstein H, Sealfon SC. Conserved helix 7 tyrosine acts as a multistate conformational switch in the 5HT2C receptor. Identification of a novel "locked-on" phenotype and double revertant mutations. J Biol Chem 2002; 277: 36577-36584.
63. Bondensgaard K, Ankersen M, Thøgersen H, Hansen BS,Wulff BS, Bywater RP. Recognition of privileged structures by G-protein coupled receptors. J Med Chem 2004; 47: 888-899.
64. Oliveira L, Paiva ACM,Vriend G. Correlated mutation analyses on very large sequence families. Chembiochem 2002; 3: 1010-1017.
65. Ritter E, Zimmermann K, Heck M, Hofmann KP, Bartl FJ. Transition of rhodopsin into the active metarhodopsin II state opens a new light-induced pathway linked to Schiff base isomerization. J Biol Chem 2004; 279: 48102-48111.
66. Vogel R, Ludeke S, Radu I, Siebert F, Sheves M. Photoreactions of metarhodopsin III. Biochemistry 2004; 43: 10255-10264.
67. Liapakis G, Chan C, Papadokostaki M, Javitch JA. Synergistic contributions of the functional groups of epinephrine to its affinity and efficacy at the beta2 adrenergic receptor. Mol Pharmacol 2004; 65: 1181-1190.
68. Baneres JL, Parello J. Structure-based analysis of GPCR function: evidence for a novel pentameric assembly between the dimeric leukotriene B4 receptor BLT1 and the G-protein. J Mol Biol 2003; 329: 815-329.
69. Hebert T, Loisel TP, Adam L, Ethier N, St. Onge S, Bouvier M. Functional rescue of a constitutively desensitized beta-2-AR through receptor dimerization. Biochem J 1998; 330: 287-293.
70. Hebert TE, Moffett S, Morello JP, Loisel TP, Bichet DG, Barret C, Bouvier M. A peptide derived from a beta2-adrenergic receptor transmembrane domain inhibits both receptor dimerization and activation. J Biol Chem 1996; 271: 16384-16392.
71. Maggio R, Barbier P, Fornai F, Corsini GU. Functional role of the third cytoplasmic loop in muscarinic receptor dimerization. J Biol Chem 1996; 271: 31055-31060.
72. Maggio R,Vogel Z,Wess J. Coexpression studies with mutant muscarinic/adrenergic receptors provide evidence for intermolecular "cross-talk" between G-protein-linked receptors. Proc Natl Acad Sci USA 1993; 90: 3103-3107.
73. Medina R, Perdomo D, Bubis J. The hydrodynamic properties of dark-and light-activated states of n-dodecyl beta-Dmaltoside-solubilized bovine rhodopsin support the dimeric structure of both conformations. J Biol Chem 2004; 279: 39565-39573.
74. Liang Y, Fotiadies D, Filipek S, Sapertstein DA, Palczewski K, Engel, A. Organization of the G-Protein coupled receptors rhodopsin and opsin in native membranes. J Biol Chem 2003; 278: 21655-21662.
75. Fotiadis D, Liang Y, Filipek S, Saperstein DA, Engel A, Palczewski K. Atomic-force microscopy: Rhodopsin dimers in native disc membranes. Nature 2003; 421: 127-128.
76. Unger VM, Schertler GFX. Low-resolution structure of bovine rhodopsin determined by electron cryomicroscopy. Biophys J 1995; 68: 1776-1786.
77. Schertler GFX,Villa C.,HendersonR. Projection structure of rhodopsin. Nature 1993; 362: 770-772.
78. Corless JM, McCaslin DR, Scott BL. Two-dimensional rhodopsin crystals from disk membranes of frog retinal rod outer segments, Proc Natl Acad Sci USA 1982; 80: 1116-1120.
79. Filizola M,Weinstein H. Structural models for dimerization of G-protein coupled receptors: the opioid receptor homodimers. Biopolymers 2002; 66: 317-325.
80. Dean MK, Higgs C, Smith R.E, Bywater RP, Snell CR, Scot PD, Upton, GJ, Howe,TJ, Reynolds, C.A. Dimerization of G-protein-coupled receptors. J Med Chem 2001; 44: 4595-4614.
81. Gouldson PR, Dean MK, Snell CR, Bywater RP, Gkoutos G, Reynolds CA. Lipid-facing correlated mutations and dimerization in G-protein coupled receptors. Protein Eng 2001; 14: 759-767.
82. Gouldson PR, Snell CR, Bywater RP, Higgs C, Reynolds CA. Domain swapping in G-protein coupled receptor dimers. Protein Eng 1998; 11: 1181-1193.
83. Lee SP, O'Dowd BF, Rajaram RD, Nguyen T, George SR. D2 dopamine receptor homodimerization is mediated by multiple sites of interaction, including an intermolecular interaction involving transmembrane domain 4. Biochemistry 2003; 42: 11023-11031.
84. Bywater RP, Sørensen A, Røgen P, Hjorth PG. Construction of the simplest model to explain complex receptor activation kinetics. J Theoret Biol 2002; 218: 139-147.
85. Fernando H, Chin C, Rosgen J, Rajarathnam K. Dimer dissociation is essential for interleukin-8 (IL-8) binding to CXCR1 receptor. J Biol Chem 2004; 279: 36175-36178.
86. Milligan G. G protein-coupled receptor dimerization: function and ligand pharmacology. Mol Pharmacol 2004; 66: 1-7.
87. Percherancier Y, Berchiche Y, Slight I,Volkmer-Engert R, Tamamura H, Fujii N, Bouvier M, Heveker N. Bioluminescence resonance energy transfer reveals ligand-induced conformational changes in CXCR4 homo-and heterodimers. J Biol Chem 2005; Jan 4: [Epub ahead of print].
88. Mandrika I, Petrovska R,Wikberg J. Melanocortin receptors form constitutive homo-and heterodimers. Biochem Biophys Res Commun 2005; 326: 349-354.
89. Rios CD, Jordan BA, Gomes I, Devi LA. G-protein-coupled receptor dimerization:modulation of receptor function. Pharmacol Ther 2001; 92: 71-87.
90. Gomes I, Jordan BA, Gupta A, Rios C, Trapaidze N, Devi LA. G-protein coupled receptor dimerization: implications in modulating receptor function. J Mol Med 2001; 79: 226-242.
91. Bakker RA, Dees G, Carrillo JJ, Booth RG, Lopez-Gimenez JF, Milligan G, Strange PG, Leurs R. Domain swapping in the human histamine H1 receptor. J Pharmacol Exp Ther 2004; 311: 131-138.
92. Javitch JA. The ants go marching two by two: oligomeric structure of G-protein-coupled receptors. Mol Pharmacol 2004; 66: 1077-1082.
93. Salahpour A, Bonin H, Bhalla S, Petaja-Repo U, Bouvier' M. Biochemical characterization of beta2-adrenergic receptor dimers and oligomers. Biol Chem 2003; 384: 117-123.
94. Heydorn A,Ward RJ, Jorgensen R, Rosenkilde MM, Frimurer TM, Milligan G, Kostenis E. Identification of a novel site within G protein alpha subunits important for specificity of receptor-G protein interaction. Mol Pharmacol 2004; 66: 250-259.
95. Kostenis E, Martini L, Ellis J, WaldhoerM, Heydorn A, Rosenkilde MM, Norregaard PK, Jorgensen R,Whistler JL, Milligan G. A highly conserved glycine within linker I and the extreme C-terminus of G protein subunits interact cooperatively in switching GPCR-to-effector specificity. J Pharmacol Exp Ther 2005; 313: 78-87.
96. Horn F,Van derWenden EM Oliveira, L Ijzerman AP,Vriend G. Receptors coupling to G proteins: is there a signal behind the sequence? Proteins, Struct, Funct Genet 2000; 41: 448-459.
97. Onrust R, Herzmark P, Chi P, Garcia PD, Lichtarge O, Kingsley C, Bourne HR. Receptor and betagamma binding sites in the alpha subunit of the retinal G protein transducin. Science 1997; 275: 381-384.
98. Lichtarge O, Bourne HR, Cohen FE. Evolutionarily conserved G alpha beta gamma binding surfaces support a model of the G protein-receptor complex. Proc Natl Acad Sci USA 1996; 93: 7507-7511.
99. Møller S,Vilo J, Croning MD. Prediction of the coupling specificity of G protein coupled receptors to their G proteins. Bioinformatics 2001; 17(Suppl 1): S174-S181.
100. Elefsinioti AL, Bagos PG, Spyropoulos IC, Hamodrakas SJ. A database for G proteins and their interaction with GPCRs. BMC Bioinformatics 2004; 5: 208.