Functional significance of serotonin receptor dimerization

Experimental Brain Research

Volumn 230, Issue 4, 2013, Pages 375-386

  Herrick Davis, Katharine ^a  

^a ALBANY MEDICAL COLLEGE   (United States)

Author keywords

Dimer interface; GPCR activation; Homodimer; Oligomer; Serotonin receptor

Indexed keywords

BIOGENIC AMINE; DIMER; G PROTEIN COUPLED RECEPTOR; GUANINE NUCLEOTIDE BINDING PROTEIN; HETERODIMER; LIGAND; OLIGOMER; SEROTONIN 1B RECEPTOR; SEROTONIN 2A RECEPTOR; SEROTONIN 2B RECEPTOR; SEROTONIN 2C RECEPTOR; SEROTONIN 4 RECEPTOR; SEROTONIN 7 RECEPTOR; SEROTONIN RECEPTOR;

ARTICLE; ASTROCYTE; BRAIN REGION; DIMERIZATION; HUMAN; LIGAND BINDING; MOLECULAR SIZE; PRIORITY JOURNAL; RECEPTOR BINDING; RECEPTOR UPREGULATION; SIGNAL TRANSDUCTION;

ANIMALS; ENZYME ACTIVATION; HUMANS; LIGANDS; PROTEIN MULTIMERIZATION; RECEPTORS, SEROTONIN; SEROTONIN;

EID: 84885628843     PISSN: 00144819     EISSN: 14321106     Source Type: Journal    
DOI: 10.1007/s00221-013-3622-1     Document Type: Article

References (107)

1. Albizu L, Cottet M, Kralikova M et al (2010) Time-resolved FRET between GPCR ligands reveals oligomers in native tissues. Nat Chem Biol 6:587-594
2. Albizu L, Holloway T, González-Maeso J, Sealfon SC (2011) Functional crosstalk and heteromerization of serotonin 5-HT2A and dopamine D2 receptors. Neuropharmacology 61:770-777
3. Alvarez-Curto E, Ward RJ, Pediani JD, Milligan G (2010) Ligand regulation of the quaternary organization of cell surface M3 muscarinic acetylcholine receptors analyzed by fluorescence resonance energy transfer (FRET) imaging and homogeneous time-resolved FRET. J Biol Chem 285:23318-23330
4. Banères JL, Parello J (2003) 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 329:815-829
5. Bayburt TH, Leitz AJ, Xie G, Oprian DD, Sligar SG (2007) Transducin activation by nanoscale lipid bilayers containing one and two rhodopsins. J Biol Chem 282:14875-14881
6. Benkirane M, Jin DY, Chun RF et al (1997) Mechanism of transdominant inhibition of CCR5-mediated HIV-1 infection by ccr5delta32. J Biol Chem 272:30603-30606
7. Berthouze M, Ayoub M, Russo O, Rivail L, Sicsic S, Fischmeister R, Berque-Bestel I, Jockers R, Lezoualc'h F (2005) Constitutive dimerization of human serotonin 5-HT4 receptors in living cells. FEBS Lett 579:2973-2980
8. Berthouze M, Rivail L, Lucas A, Ayoub MA, Russo O, Sicsic S, Fischmeister R, Berque-Bestel I, Jockers R, Lezoualc'h F (2007) Two transmembrane Cys residues are involved in 5-HT4 receptor dimerization. Biochem Biophys Res Commun 356:642-647
9. Borroto-Escuela DO, Romero-Fernandez W, Pérez-Alea M et al (2012) The existence of FGFR1-5-HT1A receptor heterocomplexes in midbrain 5-HT neurons of the rat: relevance for neuroplasticity. J Neurosci 32:6295-6303
10. Brea J, Castro M, Giraldo J, López-Giménez JF, Padín JF, Quintián F, Cadavid MI, Vilaró MT, Mengod G, Berg KA, Clarke WP, Vilardaga JP, Milligan G, Loza MI (2009) Evidence for distinct antagonist-revealed functional states of 5-hydroxytryptamine(2A) receptor homodimers. Mol Pharmacol 75:1380-1391
11. Bruno A, Beato C, Costantino G (2011) Molecular dynamics simulations and docking studies on 3D models of the heterodimeric and homodimeric 5-HT(2A) receptor subtype. Future Med Chem 3:665-681
12. 2-adrenergic G-protein-coupled receptor. Science 318:1258-1265
13. Choi SK, Green D, Ho A, Klein U, Marquess D, Taylor R, Turner SD (2008) Designing selective, high affinity ligands of 5-HT1D receptor by covalent dimerization of 5-HT1F ligands derived from 4-fluoro-N-[3-(1-methyl-4- piperidinyl)-1H-indol-5-yl]benzamide. J Med Chem 51:3609-3616
14. Cussac D, Rauly-Lestienne I, Heusler P, Finana F, Cathala C, Bernois S, De Vries L (2012) μ-opioid and 5-HT1A receptors heterodimerize and show signalling crosstalk via G protein and MAP-kinase pathways. Cell Signal 24:1648-1657
15. Damian M, Martin A, Mesnier D, Pin JP, Banères JL (2006) Asymmetric conformational changes in a GPCR dimer controlled by G-proteins. EMBO J 25:5693-5702
16. Day CA, Kenworthy KA (2009) Tracking microdomain dynamics in cell membranes. Biochim Biophys Acta 1788:245-253
17. Dorsch S, Klotz KN, Engelhardt S, Lohse MJ, Bünemann M (2009) Analysis of receptor oligomerization by FRAP microscopy. Nat Methods 6:225-230
18. Dupuis DS, Perez M, Halazy S, Colpaert FC, Pauwels PJ (1998) Magnitude of 5-HT1B and 5-HT1A receptor activation in guinea-pig and rat brain: evidence from sumatriptan dimer-mediated [35S]GTPgammaS binding responses. Brain Res Mol Brain Res 67:107-123
19. Filipek S, Krzysko KA, Fotiadis D, Liang Y, Saperstein DA, Engel A, Palczewski K (2004) A concept for G protein activation by G protein-coupled receptor dimers: the transducin/rhodopsin interface. Photochem Photobiol Sci 3:628-638
20. Fonseca JM, Lambert NA (2009) Instability of a class a G protein-coupled receptor oligomer interface. Mol Pharmacol 75:1296-1299
21. Fung JJ, Deupi X, Pardo L, Yao XY, Velez-Ruiz GA, DeVree BT, Sunahara RK, Kobilka BK (2009) Ligand-regulated oligomerization of beta2-adrenoceptors in a model lipid bilayer. EMBO J 28:3315-3328
22. Fuxe K, Borroto-Escuela DO, Romero-Fernandez W et al (2012) On the existence and function of galanin receptor heteromers in the central nervous system. Front Endocrinol 3:127
23. 1(A) receptor explored utilizing homo-FRET in live cells. Biophys J 100:361-368
24. Gilman AG (1987) G proteins: transducers of receptor-generated signals. Ann Rev Biochem 56:615-649
25. Goin JC, Nathanson NM (2006) Quantitative analysis of muscarinic acetylcholine receptor homo- and heterodimerization in live cells: regulation of receptor down-regulation by heterodimerization. J Biol Chem 281:5416-5425
26. González-Maeso J, Ang RL, Yuen T et al (2008) Identification of a serotonin/glutamate receptor complex implicated in psychosis. Nature 452:93-97
27. González-Maeso J (2011) GPCR oligomers in pharmacology and signaling. Mol Brain 4:20-27
28. González-Maeso J, Sealfon SC (2012) Functional selectivity in GPCR heterocomplexes. Mini Rev Med Chem 12:851-855
29. Gorinski N, Kowalsman N, Renner U, Wirth A, Reinartz MT, Seifert R, Zeug A, Ponimaskin E, Niv MY (2012) Computational and experimental analysis of the transmembrane domain 4/5 dimerization interface of the serotonin 5-HT(1A) receptor. Mol Pharmacol 82:448-463
30. Goudet C, Kniazeff J, Hlavackova V, Malhaire F, Maurel D, Acher F, Blahos J, Prézeau L, Pin JP (2005) Asymmetric functioning of dimeric metabotropic glutamate receptors disclosed by positive allosteric modulators. J Biol Chem 280:24380-24385
31. Guo W, Shi L, Javitch JA (2003) The fourth transmembrane segment forms the interface of the dopamine D2 receptor homodimer. J Biol Chem 278:4385-4388
32. Guo W, Shi L, Filizola M, Weinstein H, Javitch JA (2005) Crosstalk in G protein-coupled receptors: changes at the transmembrane homodimer interface determine activation. Proc Natl Acad Sci 102:17495-17500
33. Guo W, Urizar E, Kralikova M, Mobarec JC, Shi L, Filizola M, Javitch JA (2008) Dopamine D2 receptors form higher order oligomers at physiological expression levels. EMBO J 27:2293-2304
34. Gupta A, Mulder J, Gomes I, Rozenfeld R, Bushlin I, Ong E, Lim M, Maillet E, Junek M, Cahill CM, Harkany T, Devi LA (2010) Increased abundance of opioid receptor heteromers after chronic morphine administration. Sci Signal 3:ra54
35. Halazy S, Perez M, Fourrier C, Pallard I, Pauwels PJ, Palmier C, John GW, Valentin JP, Bonnafous R, Martinez J (1996) Serotonin dimers: application of the bivalent ligand approach to the design of new potent and selective 5-HT(1B/1D) agonists. J Med Chem 39:4920-4927
36. Han Y, Moreira IS, Urizar E, Weinstein H, Javitch JA (2009) Allosteric communication between protomers of dopamine class A GPCR dimers modulates activation. Nat Chem Biol 5:688-695
37. Hern JA, Baig AH, Machanov GI, Birdsall B, Corrie JET, Lazareno S, Molloy JE, Birdsall NJM (2010) Formation and dissociation of M1 muscarinic receptor dimers seen by total internal reflection fluorescence imaging of single molecules. PNAS 107:2693-2698
38. Herrick-Davis K, Grinde E, Mazurkiewicz JE (2004) Biochemical and biophysical characterization of serotonin 5-HT2C receptor homodimers on the plasma membrane of living cells. Biochemistry 43:13963-13971
39. Herrick-Davis K, Grinde E, Harrigan TJ, Mazurkiewicz JE (2005) Inhibition of serotonin 5-hydroxytryptamine2C receptor function through heterodimerization: receptor dimers bind two molecules of ligand and one G-protein. J Biol Chem 280:40144-40151
40. 2C receptor homodimer biogenesis in the endoplasmic reticulum: real-time visualization with confocal fluorescence resonance energy transfer. J Biol Chem 281:27109-27116
41. Herrick-Davis K, Grinde E, Weaver BA (2007) Serotonin 5-HT(2C) receptor homodimerization is not regulated by agonist or inverse agonist treatment. Eur J Pharmacol 568:45-53
42. 2C receptor revealed by fluorescence correlation spectroscopy with photon counting histogram analysis: evidence for homodimers without monomers or tetramers. J Biol Chem 287:23604-23614
43. Hlavackova V, Goudet C, Kniazeff J, Zikova A, Maurel D, Vol C, Trojanova J, Prézeau L, Pin JP, Blahos J (2005) Evidence for a single heptahelical domain being turned on upon activation of a dimeric GPCR. EMBO J 24:499-509
44. Huang J, Chen S, Zhang JJ, Huang XY (2013) Crystal structure of oligomeric β1-adrenergic G protein-coupled receptors in ligand-free basal state. Nat Struct Mol Biol 20:419-425
45. James JR, Oliveira MI, Carmo AM, Iaboni A, Davis SJ (2006) A rigorous experimental framework for detecting protein oligomerization using bioluminescence resonance energy transfer. Nat Methods 3:1001-1006
46. Jastrzebska B, Ringler P, Lodowski DT, Moiseenkova-Bell V, Golczak M, Müller SA, Palczewski K, Engel A (2011) Rhodopsin-transducin heteropentamer: three-dimensional structure and biochemical characterization. J Struct Biol 176:387-394
47. Jastrzebska B, Ringler P, Palczewski K, Engel A (2013a) The rhodopsin-transducin complex houses two distinct rhodopsin molecules. J Struct Biol 182:164-172
48. Jastrzebska B, Orban T, Golczak M, Engel A, Palczewski K (2013b) Asymmetry of the rhodopsin dimer in complex with transducin. FASEB J 27:1572-1584
49. Johnston JM, Wang H, Provasi D, Filizola M (2012) Assessing the relative stability of dimer interfaces in g protein-coupled receptors. PLoS Comput Biol 8:e1002649
50. Kasai RS, Suzuki KGN, Prossnitz ER, Koyama-Honda I, Nakada C, Fujiwara TK, Kusumi A (2011) Full characterization of GPCR monomer-dimer equilibrium by single molecule imaging. J Cell Biol 192:463-480
51. Knepp AM, Periole X, Marrink SJ, Sakmar TP, Huber T (2012) Rhodopsin forms a dimer with cytoplasmic helix 8 contacts in native membranes. Biochemistry 51:1819-1821
52. Kniazeff J, Bessis AS, Maurel D, Ansanay H, Prézeau L, Pin JP (2004) Closed state of both binding domains of homodimeric mGlu receptors is required for full activity. Nat Struct Mol Biol 11:706-713
53. Knight JA, Smith C, Toohey N, Klein MT, Teitler M (2009) Pharmacological analysis of the novel, rapid, and potent inactivation of the human 5-Hydroxytryptamine7 receptor by risperidone, 9-OH-Risperidone, and other inactivating antagonists. Mol Pharmacol 75:374-380
54. Kobe F, Renner U, Woehler A, Wlodarczyk J, Papusheva E, Bao G, Zeug A, Richter DW, Neher E, Ponimaskin E (2008) Stimulation- and palmitoylation- dependent changes in oligomeric conformation of serotonin 5-HT1A receptors. Biochim Biophys Acta 1783:1503-1516
55. Kren V, Eich E, Pertz HH (2004) Pergolide, terguride and N, N'-spacer-linked oligomers of both interact with 5-HT2A receptors of rat tail artery. Physiol Res 53:35-43
56. Kuang YQ, Charette N, Frazer J, Holland PJ, Attwood KM, Dellaire G, Dupre DJ (2012) Dopamine receptor-interacting protein 78 acts as a molecular chaperone for CCR5 chemokine receptor signaling complex organization. PLoS ONE 7:e40522
57. Lambert NA (2010) GPCR dimers fall apart. Sci Signal 3:12
58. Lezoualc'h F, Jockers R, Berque-Bestel I (2009) Multivalent-based drug design applied to serotonin 5-HT(4) receptor oligomers. Curr Pharm Des 15:719-729
59. Liang Y, Fotiadis D, Filipek S et al (2003) Organization of the G protein-coupled receptors rhodopsin and opsin in native membranes. J Biol Chem 278:21655-21662
60. Lodowski DT, Salom D, LeTrong IL et al (2007) Crystal packing analysis of rhodopsin crystals. J Struct Biol 158:455-462
61. Lopez-Gimenez JF, Canals M, Pediani JD, Milligan G (2007) The alpha1b-adrenoceptor exists as a higher-order oligomer: effective oligomerization is required for receptor maturation, surface delivery, and function. Mol Pharmacol 71:1015-1029
62. Łukasiewicz S, Błasiak E, Faron-Górecka A, Polit A, Tworzydło M, Górecki A, Wasylewski Z, Dziedzicka-Wasylewska M (2007) Fluorescence studies of homooligomerization of adenosine A2A and serotonin 5-HT1A receptors reveal the specificity of receptor interactions in the plasma membrane. Pharmacol Rep 59:379-392
63. Łukasiewicz S, Faron-Górecka A, Keodracka-Krok S, Dziedzicka-Wasylewska M (2011) Effect of clozapine on the dimerization of serotonin 5-HT(2A) receptor and its genetic variant 5-HT(2A)H425Y with dopamine D(2) receptor. Eur J Pharmacol 659:114-123
64. Mancia F, Assur Z, Herman AG et al (2008) Ligand sensitivity in dimeric associations of the serotonin 5HT2c receptor. EMBO Rep 9:363-369
65. Manglik A, Kruse AC, Kobilka TS et al (2012) Crystal structure of the μ-opioid receptor bound to a morphinan antagonist. Nature 485:321-326
66. Maurice P, Kamal M, Jockers R (2011) Asymmetry of GPCR oligomers supports their functional relevance. Trends Pharmacol Sci 32:514-520
67. Mercier JF, Salahpour A, Angers S, Breit A, Bouvier M (2002) Quantitative assessment of beta 1- and beta 2-adrenergic receptor homo- and heterodimerization by bioluminescence resonance energy transfer. J Biol Chem 277:44925-44931
68. Meyer BH, Segura JM, Martinez KL, Hovius R, George N, Johnsson K, Vogel H (2006) FRET imaging reveals that functional neurokinin-1 receptors are monomeric and reside in membrane microdomains of live cells. Proc Natl Acad Sci 103:2138-2143
69. Milligan G (2008) G protein-coupled receptor dimerisation: molecular basis and relevance to function. Biochim Biophys Acta 1768:825-835
70. Milligan G (2010) The role of dimerisation in the cellular trafficking of G-protein-coupled receptors. Curr Opin Pharmacol 10:23-29
71. Moreno JL, Holloway T, Albizu L, Sealfon SC, González-Maeso J (2011) Metabotropic glutamate mGlu2 receptor is necessary for the pharmacological and behavioral effects induced by hallucinogenic 5-HT2A receptor agonists. Neurosci Lett 493:76-79
72. Moreno JL, Muguruza C, Umali A et al (2012) Identification of three residues essential for 5-hydroxytryptamine 2A-metabotropic glutamate 2 (5-HT2A mGlu2) receptor heteromerization and its psychoactive behavioral function. J Biol Chem 287:44301-44319
73. Murakami M, Kouyama T (2008) Crystal structure of squid rhodopsin. Nature 453:363-367
74. O'Dowd BF, Ji X, Alijaniaram M, Nguyen T, George SR (2011) Separation and reformation of cell surface dopamine receptor oligomers visualized in cells. Eur J Pharmacol 658:74-83
75. Paila YD, Kombrabail M, Krishnamoorthy G, Chattopadhyay A (2011) Oligomerization of the serotonin(1A) receptor in live cells: a time-resolved fluorescence anisotropy approach. J Phys Chem B 115:11439-11447
76. Patowary S, Alvarez-Curto E, Xu TR, Holz JD, Oliver JA, Milligan G, Raicu V (2013) The Muscarinic M3 Acetylcholine receptor exists as two differently sized complexes at the plasma membrane. Biochem J 452:303-312
77. Pauwels PJ, Dupuis DS, Perez M, Halazy S (1998) Dimerization of 8-OH-DPAT increases activity at serotonin 5-HT1A receptors. Naunyn Schmiedebergs Arch Pharmacol 358:404-410
78. Pellissier LP, Barthet G, Gaven F, Cassier E, Trinquet E, Pin JP, Marin P, Dumuis A, Bockaert J, Bane'res JL, Claeysen S (2011) G protein activation by serotonin type 4 receptor dimers: evidence that turning on two protomers is more efficient. J Biol Chem 286:9985-9997
79. Perez M, Pauwels PJ, Fourrier C, Chopin P, Valentin JP, John GW, Marien M, Halazy S (1998) Dimerization of sumatriptan as an efficient way to design a potent, centrally and orally active 5-HT1B agonist. Bioorg Med Chem Lett 8:675-680
80. Periole X, Knepp AM, Sakmar TP, Marrink SJ, Huber T (2012) Structural determinants of the supramolecular organization of G protein-coupled receptors in bilayers. J Am Chem Soc 134:10959-10965
81. 2 muscarinic receptor in live cells as determined by quantitative fluorescence resonance energy transfer. J Biol Chem 285:16723-16738
82. Rasmussen SG, DeVree BT, Zou Y, Kruse AC, Chung KY, Kobilka TS, Thian FS, Chae PS, Pardon E, Calinski D, Mathiesen JM, Shah ST, Lyons JA, Caffrey M, Gellman SH, Steyaert J, Skiniotis G, Weis WI, Sunahara RK, Kobilka BK (2011) Crystal structure of the β2 adrenergic receptor-Gs protein complex. Nature 477:549-555
83. Renner U, Zeug A, Woehler A, Niebert M, Dityatev A, Dityateva G, Gorinski N, Guseva D, Abdel-Galil D, Fröhlich M, Döring F, Wischmeyer E, Richter DW, Neher E, Ponimaskin EG (2012) Heterodimerization of serotonin receptors 5-HT1A and 5-HT7 differentially regulates receptor signalling and trafficking. J Cell Sci 125:2486-2499
84. Rivero-Müller A, Chou YY, Ji I, Lajic S, Hanyaloglu AC, Jonas K, Rahman N, Ji TH, Huhtaniemi I (2010) Rescue of defective G protein-coupled receptor function in vivo by intermolecular cooperation. Proc Natl Acad Sci 107:2319-2324
85. Rives ML, Vol C, Fukazawa Y, Tinel N, Trinquet E, Ayoub MA, Shigemoto R, Pin JP, Prézeau L (2009) Crosstalk between GABAB and mGlu1a receptors reveals new insight into GPCR signal integration. EMBO J 28:2195-2208
86. Rozenfeld R, Devi LA (2011) Exploring a role for heteromerization in GPCR signalling specificity. Biochem J 433:11-18
87. Russo O, Berthouze M, Giner M, Soulier JL, Rivail L, Sicsic S, Lezoualc'h F, Jockers R, Berque-Bestel I (2007) Synthesis of specific bivalent probes that functionally interact with 5-HT(4) receptor dimers. J Med Chem 50:4482-4492
88. Salahpour A, Angers S, Mercier JF et al (2004) Homodimerization of the beta 2-adrenergic receptor as a pre-requisite for cell surface targeting. J Biol Chem 279:33390-33397
89. Salim K, Fenton T, Bacha J, Urien-Rodriguez H, Bonnert T, Skynner HA, Watts E, Kerby J, Heald A, Beer M, McAllister G, Guest PC (2002) Oligomerization of G-protein-coupled receptors shown by selective co-immunoprecipitation. J Biol Chem 277:15482-15485
90. Scheerer P, Park JH, Hildebrand PW et al (2008) Crystal structure of opsin in its G protein-interacting conformation. Nature 455:497-502
91. Shashack MJ, Cunningham KA, Seitz PK, McGinnis A, Smith T, Watson CS, Gilbertson SR (2011) Synthesis and evaluation of dimeric derivatives of 5-HT(2A) receptor (5-HT(2A)R) antagonist M-100907. ACS Chem Neurosci 2:640-644
92. 7 receptors: evidence for in situ G protein-coupled receptor homodimer protomer cross-talk. Mol Pharmacol 79:318-325
93. Teitler M, Toohey N, Knight JA, Klein MT, Smith C (2010) Clozapine and other competitive antagonists reactivate risperidone-inactivated h5-HT7 receptors: radioligand binding and functional evidence for GPCR homodimer protomer interactions. Psychopharmacology 212:687-697
94. Teitler M, Klein MT (2012) A new approach for studying GPCR dimers: drug-induced inactivation and reactivation to reveal GPCR dimer function in vitro, in primary culture, and in vivo. Pharmacol Ther 133:205-217
95. Terrillon S, Durroux T, Mouillac B et al (2003) Oxytocin and vasopressin V1a and V2 receptors form constitutive homo- and heterodimers during biosynthesis. Mol Endocrin 17:677-691
96. Vilardaga JP, Nikolaev VO, Lorenz K, Ferrandon S, Zhuang Z, Lohse MJ (2008) Conformational cross-talk between alpha2A-adrenergic and mu-opioid receptors controls cell signaling. Nat Chem Biol 4:126-131
97. Wacker D, Wang C, Katritch V, Han GW, Huang XP, Vardy E, McCorvy JD, Jiang Y, Chu M, Siu FY, Liu W, Xu HE, Cherezov V, Roth BL, Stevens RC (2013) Structural features for functional selectivity at serotonin receptors. Science 340:615-619
98. Wang C, Jiang Y, Ma J, Wu H, Wacker D, Katritch V, Han GW, Liu W, Huang XP, Vardy E, McCorvy JD, Gao X, Zhou XE, Melcher K, Zhang C, Bai F, Yang H, Yang L, Jiang H, Roth BL, Cherezov V, Stevens RC, Xu HE (2013) Structural basis for molecular recognition at serotonin receptors. Science 340:610-614
99. Wertman J, Dupré DJ (2013) G protein-coupled receptor dimers: look like their parents, but act like teenagers! J Recept Signal Transduct Res 33:135-138
100. Westfield GH, Rasmussen SG, Su M, Dutta S, DeVree BT, Chung KY, Calinski D, Velez-Ruiz G, Oleskie AN, Pardon E, Chae PS, Liu T, Li S, Woods VL Jr, Steyaert J, Kobilka BK, Sunahara RK, Skiniotis G (2011) Structural flexibility of the G alpha s alpha-helical domain in the beta2-adrenoceptor Gs complex. Proc Natl Acad Sci 108:16086-16091
101. White JH, Wise A, Main MJ et al (1998) Heterodimerization is required for the formation of a functional GABA(B) receptor. Nature 396:679-682
102. Whorton MR, Bokoch MP, Rasmussen SG, Huang B, Zare RN, Kobilka B, Sunahara RK (2007) A monomeric G protein-coupled receptor isolated in a high-density lipoprotein particle efficiently activates its G protein. Proc Natl Acad Sci 104:7682-7687
103. Woehler A, Wlodarczyk J, Ponimaskin EG (2009) Specific oligomerization of the 5HT1A receptor in the plasma membrane. Glycoconj J 26:749-756
104. Wu B, Chien EY, Mol CD et al (2010) Structures of the CXCR4 chemokine GPCR with small-molecule and cyclic peptide antagonists. Science 330:1066-1071
105. Wu H, Wacker D, Mileni M et al (2012) Structure of the human κ-opioid receptor in complex with JDTic. Nature 21:327-332
106. Xie Z, Lee SP, O'Dowd BF, George SR (1999) Serotonin 5-HT1B and 5-HT1D receptors form homodimers when expressed alone and heterodimers when co-expressed. FEBS Lett 456:63-67
107. Zhu X, Wess J (1998) Truncated V2 vasopressin receptors as negative regulators of wild-type V2 receptor function. Biochemistry 37:15773-15784