Skip to main content
SpringerLink
Log in

GPCRs: Past, present, and future

  • Chapter
Structural Bioinformatics of Membrane Proteins

Abstract

The family of G-protein-coupled receptors (GPCRs) is by far the best-studied family among the integral membrane proteins, because it represents the largest and most important group for therapeutics. In this chapter we provide an overview of the major developments in the GPCR field since the 19th century, and we shed some light on some of the questions that are relevant now and those that need to be answered in the future regarding GPCR structure and function.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Benovic JL, Kühn H, Weyand I, Codina J, Caron MG, Lefkowitz J (1987) Functional desensitization of the isolated beta-adrenergic receptor by the beta-adrenergic receptor kinase: potential role of an analog of the retinal protein arrestin (48-kDa protein). Proc Natl Acad Sci USA 84: 8879–8882

    Article  Google Scholar 

  • Bond R and Ijzerman AP (2006) Recent developments in constitutive receptor activity and inverse agonism, and their potential for GPCR drug discovery. Trends Pharmacol Sci 27: 92–96

    Article  Google Scholar 

  • Bond R, Leff P, Johnson TD, Milano CA, Rockman HA, McMinn TR, Apparsundaram S, Hyek MF, Kenakin TP, Allen LF (1995) Physiological effects of inverse agonists in transgenic mice with myocardial overexpression of the beta 2-adrenoceptor. Nature 374: 272–276

    Article  Google Scholar 

  • Brézillon S, Detheux M, Parmentier M, Hökfelt T, Hurd YL (2001) Distribution of an orphan G-protein coupled receptor (JP05) mRNA in the human brain. Brain Res 921: 21–30

    Article  Google Scholar 

  • Brézillon S, Lannoy V, Franssen J, Le Poul E, Dupriez V, Lucchetti J, Detheux M, Parmentier M (2003) Identification of natural ligands for the orphan G-protein-coupled receptors GPR7 and GPR8. J Biol Chem 278: 776–783

    Article  Google Scholar 

  • Bywater RP (2005) Location and nature of the residues important for ligand recognition in G-protein coupled receptors. J Mol Recognit 18: 60–72

    Article  Google Scholar 

  • Caron MG, Srinivasan Y, Pitha J, Kociolek K, Lefkowitz RJ (1979) Affinity chromatography of the beta-adrenergic receptor. J Biol Chem 254: 2923–2927

    Google Scholar 

  • Cerione R, Strulovici B, Benovic JL, Strader CD, Caron MG, Lefkowitz RJ (1983) Reconstitution of beta-adrenergic receptors in lipid vesicles: affinity chromatography-purified receptors confer catecholamine responsiveness on a heterologous adenylate cyclase system. Proc Natl Acad Sci USA 80: 4899–4903

    Article  Google Scholar 

  • Cerione R, Sibley DR, Codina J, Benovic JL, Winslow J, Neer EJ, Birnbaumer L, Caron MG, Lefkowitz RJ (1984) Reconstitution of a hormone-sensitive adenylate cyclase system. The pure beta-adrenergic receptor and guanine nucleotide regulatory protein confer hormone responsiveness on the resolved catalytic unit. J Biol Chem 259: 9979–9982

    Google Scholar 

  • Cherezov V, Rosenbaum DM, Hanson MA, Rasmussen SGF, Tian FS, Kobilka TS, Choi H, Kuhn P, Weis WI, Kobilka BK, Stevens RC (2007) High-resolution crystal structure of an engineered human beta2-adrenergic G-protein-coupled receptor. Science 318: 1258–1265

    Article  Google Scholar 

  • Conn PM, Rogers DC, McNeil R (1982a) Potency enhancement of a GnRH agonist: GnRH-receptor microaggregation stimulates gonadotropin release. Endocrinology 111: 335–337

    Article  Google Scholar 

  • Conn PM, Rogers DC, Stewart JM, Niedel J, Shefield T (1982b) Conversion of a gonadotropin-releasing hormone antagonist to an agonist. Nature 296: 653–655

    Article  Google Scholar 

  • Conn PJ, Christopoulos A, Lindsley CW (2009) Allosteric modulators of GPCRs: a novel approach for the treatment of CNS disorders. Nat Rev Drug Discov 8: 41–54

    Article  Google Scholar 

  • Costa T and Herz A (1989) Antagonists with negative intrinsic activity at delta opioid receptors coupled to GTP-binding proteins. Proc Natl Acad Sci USA 86: 7321–7325

    Article  Google Scholar 

  • Costa T, Ogino Y, Munson PJ, Onaran HO, Rodbard D (1992) Drug efficacy at guanine nucleotidebinding regulatory protein-linked receptors: thermodynamic interpretation of negative antagonism and of receptor activity in the absence of ligand. Mol Pharmacol41: 549–560

    Google Scholar 

  • Cotecchia S, Ostrowski J, Kjelsberg MA, Caron MG, Lefkowitz RJ (1992) Discrete amino acid sequences of the alpha 1-adrenergic receptor determine the selectivity of coupling to phosphatidylinositol hydrolysis. J Biol Chem 267: 1633–1639

    Google Scholar 

  • Dahl SG, Edvardsen O, Sylte I (1991) Molecular dynamics of dopamine at the D2 receptor. Proc Natl Acad Sci USA 88: 8111–8115

    Article  Google Scholar 

  • De Lean A, Stadel JM, Lefkowitz RJ (1980) A ternary complex model explains the agonist-specific binding properties of the adenylate cyclase-coupled beta-adrenergic receptor. J Biol Chem 255: 7108–7117

    Google Scholar 

  • Dean MK, Higgs C, Smith RE, Bywater RP, Snell CR, Scot PD, Upton GJ, Howe TJ, Reynolds CA (2001) Dimerization of G-protein-coupled receptors. J Med Chem 44: 4595–4614

    Article  Google Scholar 

  • Dixon R, Kobilka BK, Strader DJ, Benovic JL, Dohlman HG, Frielle T, Bolanowski MA, Bennett CD, Rands E, Diehl RE, Mumford R, Slater EE, Sigal IS, Caron MG, Lefkowitz RJ, Strader CD (1986) Cloning of the gene and cDNA for mammalian beta-adrenergic receptor and homology with rhodopsin. Nature 321: 75–79

    Article  Google Scholar 

  • Donnelly D and Findlay JB (1994) Seven-helix receptors: structure and modelling. Curr Opin Struct Biol 4: 582–589

    Article  Google Scholar 

  • Fanelli F, Menziani C, Scheer A, Cotecchia S, De Benedetti PG (1999) Theoretical study of the electrostatically driven step of receptor-G-protein recognition. Proteins 37: 145–156

    Article  Google Scholar 

  • Fargin A, Raymond JR, Lohse MJ, Kobilka BK, Caron MG, Lefkowitz RJ (1988) The genomic clone G-21 which resembles a beta-adrenergic receptor sequence encodes the 5-HT1A receptor. Nature 335: 358–360

    Article  Google Scholar 

  • Farrens DL, Altenbach C, Yang K, Hubbell WL, Khorana HG (1996) Requirement of rigid-body motion of transmembrane helices for light activation of rhodopsin. Science 274: 768–770

    Article  Google Scholar 

  • Fotiadis D, Liang Y, Filipek S, Saperstein DA, Engel A, Palczewski K (2003) Atomic-force microscopy: rhodopsin dimers in native disc membranes. Nature 421: 127–128

    Article  Google Scholar 

  • van Galen PJ, van Bergen AH, Gallo-Rodriguez C, Melman N, Olah ME, Ijzerman A P, Stiles GL, Jacobson KA (1994) A binding site model and structure-activity relationships for the rat A3 adenosine receptor. Mol Pharmacol45: 1101–1111

    Google Scholar 

  • Gilman AG (1987) G-proteins: transducers of receptor-generated signals. Ann Rev Biochem 56: 615–649

    Article  Google Scholar 

  • Hamm HE (1998) The many faces of G-protein signaling. J Biol Chem 273: 669–672

    Article  Google Scholar 

  • Hanson MA, Cherezov V, Griffith MT, Roth CB, Jaakola V, Chien EYT, Velasquez J, Kuhn P, Stevens RC (2008) A specific cholesterol binding site is established by the 2.8 A structure of the human beta2-adrenergic receptor. Structure 16: 897–905

    Article  Google Scholar 

  • Hanyaloglu AC and von Zastrow M (2008) Regulation of GPCRs by endocytic membrane trafficking and its potential implications. Ann Rev Pharmacol Toxicol 48: 537–568

    Article  Google Scholar 

  • Hargrave PA, McDowell JH, Curtis DR, Wang JK, Juszczak E, Fong SL, Rao JK, Argos P (1983) The structure of bovine rhodopsin. Biophys Struct Mech 9: 235–244

    Article  Google Scholar 

  • Hebert TE, Moffett S, Morello JP, Loisel TP, Bichet DG, Barret C, Bouvier M (1996) A peptide derived from a beta2-adrenergic receptor transmembrane domain inhibits both receptor dimerization and activation. J Biol Chem 271: 16384–16392

    Article  Google Scholar 

  • Henderson R and Unwin PN (1975) Three-dimensional model of purple membrane obtained by electron microscopy. Nature 257: 28–32

    Article  Google Scholar 

  • Henderson R, Baldwin JM, Ceska TA, Zemlin F, Beckmann E, Downing KH (1990) Model for the structure of bacteriorhodopsin based on high-resolution electron cryo-microscopy. J Mol Biol 213: 899–929

    Article  Google Scholar 

  • Hébert TE and Bouvier M (1998) Structural and functional aspects of G-protein-coupled receptor oligomerization. Biochem Cell Biol 76: 1–11

    Article  Google Scholar 

  • Hibert MF, Trumpp-Kallmeyer S, Bruinvels A, Hoflack J (1991) Three-dimensional models of neurotransmitter G-binding protein-coupled receptors. Mol Pharmacol 40: 8–15

    Google Scholar 

  • Horn F, Bywater R, Krause G, Kuipers W, Oliveira L, Paiva AC, Sander C, Vriend G (1998) The interaction of class B G-protein-coupled receptors with their hormones. Receptors Channels 5: 305–314

    Google Scholar 

  • Horn F, Bettler E, Oliveira L, Campagne F, Cohen FE, Vriend G (2003) GPCRDB information system for G-protein-coupled receptors. Nucleic Acids Res 31: 294–297

    Article  Google Scholar 

  • Hornak V, Ahuja S, Eilers M, Goncalves JA, Sheves M, Reeves PJ, Smith SO (2010) Light activation of rhodopsin: insights from molecular dynamics simulations guided by solid-state NMR distance restraints. J Mol Biol 396(3): 510–527

    Article  Google Scholar 

  • Howard MJ, Hughes RJ, Motulsky HJ, Mullen MD, Insel PA (1987) Interactions of amiloride with alpha-and beta-adrenergic receptors: amiloride reveals an allosteric site on alpha 2-adrenergic receptors. Mol Pharmacol 32: 53–58

    Google Scholar 

  • Jaakola V, Griffith MT, Hanson MA, Cherezov V, Chien EYT, Lane JR, Ijzerman A P, Stevens RC (2008) The 2.6 Angstrom crystal structure of a human A2A adenosine receptor bound to an antagonist. Science 322: 1211–1217

    Article  Google Scholar 

  • Katritch V, Reynolds K, Cherezov V, Hanson MA, Roth CB, Yeager M, Abagyan R (2009) Analysis of full and partial agonists binding to beta2-adrenergic receptor suggests a role of transmembrane helix V in agonist-specific conformational changes. J Mol Recognit 22: 307–318

    Article  Google Scholar 

  • Kenakin T (2001) Inverse, protean, and ligand-selective agonism: matters of receptor conformation. FASEB J 15: 598–611

    Article  Google Scholar 

  • Kenakin T (2002) Efficacy at G-protein-coupled receptors. Nat Rev Drug Discov 1: 103–110

    Article  Google Scholar 

  • Kent RS, De Lean A, Lefkowitz RJ (1980) A quantitative analysis of beta-adrenergic receptor interactions: resolution of high and low affinity states of the receptor by computer modeling of ligand binding data. Mol Pharmacol 17: 14–23

    Google Scholar 

  • Kim J, Jiang Q, Glashofer M, Yehle S, Wess J, Jacobson K (1996) Glutamate residues in the second extracellular loop of the human A2a adenosine receptor are required for ligand recognition. Mol Pharmacol 49: 683–691

    Google Scholar 

  • Kim J, Altenbach C, Kono M, Oprian DD, Hubbell WL, Khorana HG (2004) Structural origins of constitutive activation in rhodopsin: role of the K296/E113 salt bridge. Proc Natl Acad Sci USA 101: 12508–12513

    Article  Google Scholar 

  • Kjelsberg MA, Cotecchia S, Ostrowski J, Caron MG, Lefkowitz RJ (1992) Constitutive activation of the alpha 1B-adrenergic receptor by all amino acid substitutions at a single site. Evidence for a region which constrains receptor activation. J Biol Chem 267: 1430–1433

    Google Scholar 

  • Kobilka BK and Deupi X (2007) Conformational complexity of G-protein-coupled receptors. Trends Pharmacol Sci 28: 397–406

    Article  Google Scholar 

  • Kobilka BK, Frielle T, Collins S, Yang-Feng T, Kobilka TS, Francke U, Lefkowitz RJ, Caron MG (1987a) An intronless gene encoding a potential member of the family of receptors coupled to guanine nucleotide regulatory proteins. Nature 329: 75–79

    Article  Google Scholar 

  • Kobilka BK, Frielle T, Dohlman HG, Bolanowski MA, Dixon R, Keller P, Caron MG, Lefkowitz RJ (1987b) Delineation of the intronless nature of the genes for the human and hamster beta 2-adrenergic receptor and their putative promoter regions. J Biol Chem 262: 7321–7327

    Google Scholar 

  • Kobilka BK, Matsui H, Kobilka TS, Yang-Feng TL, Francke U, Caron MG, Lefkowitz RJ, Regan JW (1987c) Cloning, sequencing, and expression of the gene coding for the human platelet alpha 2-adrenergic receptor. Science 238: 650–656

    Article  Google Scholar 

  • Kovacs JJ, Hara MR, Davenport CL, Kim J, Lefkowitz RJ (2009) Arrestin development: emerging roles for beta-arrestins in developmental signaling pathways. Dev Cell 17: 443–458

    Article  Google Scholar 

  • Langley JN (1905) On the reaction of cells and of nerve-endings to certain poisons, chiefly as regards the reaction of striated muscle to nicotine and to curari. J Physiol 33: 374–413

    Google Scholar 

  • Lefkowitz RJ, Cotecchia S, Samama P, Costa T (1993) Constitutive activity of receptors coupled to guanine nucleotide regulatory proteins. Trends Pharmacol Sci 14: 303–307

    Article  Google Scholar 

  • Libert F, Parmentier M, Lefort A, Dinsart C, Van Sande J, Maenhaut C, Simons MJ, Dumont JE, Vassart G (1989) Selective amplification and cloning of four new members of the G-protein-coupled receptor family. Science 244: 569–572

    Article  Google Scholar 

  • Libert F, Vassart G, Parmentier M (1991) Current developments in G-protein-coupled receptors. Curr Opin Cell Biol 3: 218–223

    Article  Google Scholar 

  • Limbird LE, Meyts PD, Lefkowitz RJ (1975) Beta-adrenergic receptors: evidence for negative cooperativity. Biochem Biophys Res Commun 64: 1160–1168

    Article  Google Scholar 

  • Lohse MJ, Benovic JL, Codina J, Caron MG, Lefkowitz RJ (1990) beta-Arrestin: a protein that regulates beta-adrenergic receptor function. Science 248: 1547–1550

    Article  Google Scholar 

  • Maehle A (2004) “Receptive substances”: John Newport Langley (1852–1925) and his path to a receptor theory of drug action. Med Hist 48: 153–174

    Google Scholar 

  • May DC, Ross EM, Gilman AG, Smigel MD (1985) Reconstitution of catecholamine-stimulated adenylate cyclase activity using three purified proteins. J Biol Chem 260: 15829–15833

    Google Scholar 

  • Mickey J, Tate R, Lefkowitz RJ (1975) Subsensitivity of adenylate cyclase and decreased beta-adrenergic receptor binding after chronic exposure to (minus)-isoproterenol in vitro. J Biol Chem 250: 5727–5729

    Google Scholar 

  • Mills A and Duggan MJ (1994) Orphan seven transmembrane domain receptors: reversing pharmacology. Trends Biotechnol 12: 47–49

    Article  Google Scholar 

  • Mukherjee C, Caron MG, Coverstone M, Lefkowitz RJ (1975) Identification of adenylate cyclase-coupled beta-adrenergic receptors in frog erythrocytes with (minus)-[3-H] alprenolol. J Biol Chem 250: 4869–4876

    Google Scholar 

  • Oliveira L, Paiva AC, Sander C, Vriend G (1994) A common step for signal transduction in G-proteincoupled receptors. Trends Pharmacol Sci 15: 170–172

    Article  Google Scholar 

  • Oliveira L, Paiva AC, Vriend G (1999) A low resolution model for the interaction of G-proteins with G-protein-coupled receptors. Protein Eng 12: 1087–1095

    Article  Google Scholar 

  • Oliveira L, Hulsen T, Lutje Hulsik D, Paiva ACM, Vriend G (2004) Heavier-than-air flying machines are impossible. FEBS Lett 564: 269–273

    Article  Google Scholar 

  • Ostrowski J, Kjelsberg MA, Caron MG, Lefkowitz RJ (1992) Mutagenesis of the beta 2-adrenergic receptor: how structure elucidates function. Ann Rev Pharmacol Toxicol 32: 167–183

    Google Scholar 

  • Ovchinnikov YuA (1982) Rhodopsin and bacteriorhodopsin: structure-function relationships. FEBS Lett 148: 179–191

    Article  Google Scholar 

  • Overington JP, Al-Lazikani B, Hopkins AL (2006) How many drug targets are there? Nat Rev Drug Discov 5: 993–996

    Article  Google Scholar 

  • Palczewski K, Kumasaka T, Hori T, Behnke CA, Motoshima H, Fox BA, Le Trong I, Teller DC, Okada T, Stenkamp RE, Yamamoto M, Miyano M (2000) Crystal structure of rhodopsin: a G-protein-coupled receptor. Science 289: 739–745

    Article  Google Scholar 

  • Pardo L, Ballesteros JA, Osman R, Weinstein H (1992) On the use of the transmembrane domain of bacteriorhodopsin as a template for modeling the three-dimensional structure of guanine nucleotide-binding regulatory protein-coupled receptors. Proc Natl Acad Sci USA 89: 4009–4012

    Article  Google Scholar 

  • Parmentier M and Detheux M (2006) Deorphanization of G-protein-coupled receptors. Ernst Schering Found Symp Proc 2: 163–186

    Article  Google Scholar 

  • Pepitoni S, Wood IC, Buckley NJ (1997) Structure of the m1 muscarinic acetylcholine receptor gene and its promoter. J Biol Chem 272: 17112–17117

    Article  Google Scholar 

  • Pert CB and Snyder SH (1973) Opiate receptor: demonstration in nervous tissue. Science 179: 1011–1014

    Article  Google Scholar 

  • Pitcher JA, Freedman NJ, Lefkowitz RJ (1998) G-protein-coupled receptor kinases. Ann Rev Biochem 67: 653–692

    Article  Google Scholar 

  • Rall TW and Sutherland EW (1958) Formation of a cyclic adenine ribonucleotide by tissue particles. J Biol Chem 232: 1065–1076

    Google Scholar 

  • Rasmussen SGF, Choi H, Rosenbaum DM, Kobilka TS, Thian FS, Edwards PC, Burghammer M, Ratnala VRP, Sanishvili R, Fischetti RF, Schertler GFX, Weis WI, Kobilka BK (2007) Crystal structure of the human beta2 adrenergic G-protein-coupled receptor. Nature 450: 383–387

    Article  Google Scholar 

  • Ritter SL and Hall R (2009) Fine-tuning of GPCR activity by receptor-interactinG-proteins. Nat Rev Mol Cell Biol 10: 819–830

    Article  Google Scholar 

  • Rodbell M, Birnbaumer L, Pohl SL, Krans HM (1971) The glucagon-sensitive adenyl cyclase system in plasma membranes of rat liver. V. An obligatory role of guanylnucleotides in glucagon action. J Biol Chem 246: 1877–1882

    Google Scholar 

  • Rognan D (2006) Ligand design for G-protein-coupled receptors. Wiley-VCH

    Google Scholar 

  • Ross EM and Gilman AG (1977) Resolution of some components of adenylate cyclase necessary for catalytic activity. J Biol Chem 252: 6966–6969

    Google Scholar 

  • Savarese TM, Wang CD, Fraser CM (1992) Site-directed mutagenesis of the rat m1 muscarinic acetylcholine receptor. Role of conserved cysteines in receptor function. J Biol Chem 267: 11439–11448

    Google Scholar 

  • Scheerer P, Park JH, Hildebrand PW, Kim YJ, Krauss N, Choe H, Hofmann KP, Ernst OP (2008) Crystal structure of opsin in its G-protein-interacting conformation. Nature 455: 497–502

    Article  Google Scholar 

  • Scholl DJ and Wells JN (2000) Serine and alanine mutagenesis of the nine native cysteine residues of the human A(1) adenosine receptor. Biochem Pharmacol 60: 1647–1654

    Article  Google Scholar 

  • Seifert R and Wenzel-Seifert K (2002) Constitutive activity of G-protein-coupled receptors: cause of disease and common property of wild-type receptors. Naunyn Schmiedeberg’s Arch Pharmacol 366: 381–416

    Article  Google Scholar 

  • Shi L and Javitch JA (2002) The binding site of aminergic G-protein-coupled receptors: the transmembrane segments and second extracellular loop. Ann Rev Pharmacol Toxicol 42: 437–467

    Article  Google Scholar 

  • Shi L and Javitch JA (2004) The second extracellular loop of the dopamine D2 receptor lines the binding-site crevice. Proc Natl Acad Sci USA 101: 440–445

    Article  Google Scholar 

  • Shi L, Liapakis G, Xu R, Guarnieri F, Ballesteros JA, Javitch JA (2002) Beta2 adrenergic receptor activation. Modulation of the proline kink in transmembrane 6 by a rotamer toggle switch. J Biol Chem 277: 40989–40996

    Article  Google Scholar 

  • Stadel JM, Nambi P, Shorr RG, Sawyer DF, Caron MG, Lefkowitz RJ (1983) Catecholamine-induced desensitization of turkey erythrocyte adenylate cyclase is associated with phosphorylation of the beta-adrenergic receptor. Proc Natl Acad Sci USA 80: 3173–3177

    Article  Google Scholar 

  • Strader CD, Fong TM, Tota MR, Underwood D, Dixon R (1994) Structure and function of G-protein-coupled receptors. Ann Rev Biochem 63: 101–132

    Article  Google Scholar 

  • Sunahara RK, Niznik HB, Weiner DM, Stormann TM, Brann MR, Kennedy JL, Gelernter JE, Rozmahel R, Yang YL, Israel Y (1990) Human dopamine D1 receptor encoded by an intronless gene on chromosome 5. Nature 347: 80–83

    Article  Google Scholar 

  • Sutherland EW and Rall TW (1958) Fractionation and characterization of a cyclic adenine ribonucleotide formed by tissue particles. J Biol Chem 232: 1077–1091

    Google Scholar 

  • Tobin AB (2008) G-protein-coupled receptor phosphorylation: where, when and by whom. Br J Pharm 153(Suppl 1): S167–S176

    Google Scholar 

  • Townsend-Nicholson A and Schofield PR (1994) A threonine residue in the seventh transmembrane domain of the human A1 adenosine receptor mediates specific agonist binding. J Biol Chem 269: 2373–2376

    Google Scholar 

  • Walsh DA, Perkins JP, Krebs EG (1968) An adenosine 3′,5′-monophosphate-dependant protein kinase from rabbit skeletal muscle. J Biol Chem 243: 3763–3765

    Google Scholar 

  • Warne T, Serrano-Vega MJ, Baker JG, Moukhametzianov R, Edwards PC, Henderson R, Leslie AGW, Tate CG, Schertler GFX (2008) Structure of a beta1-adrenergic G-protein-coupled receptor. Nature 454: 486–491

    Article  Google Scholar 

  • Wilden U and Kühn H (1982) Light-dependent phosphorylation of rhodopsin: number of phosphorylation sites. Biochemistry 21: 3014–3022

    Article  Google Scholar 

  • Wilden U, Hall SW, Kühn H (1986) Phosphodiesterase activation by photoexcited rhodopsin is quenched when rhodopsin is phosphorylated and binds the intrinsic 48-kDa protein of rod outer segments. Proc Natl Acad Sci USA 83: 1174–1178

    Article  Google Scholar 

  • Wurch T and Pauwels PJ (2000) Coupling of canine serotonin 5-HT(1B) and 5-HT(1D) receptor ubtypes to the formation of inositol phosphates by dual interactions with endogenous G(i/o) and recombinant G(alpha15) proteins. J Neurochem 75: 1180–1189

    Article  Google Scholar 

  • Yamamura HI and Snyder SH (1974) Muscarinic cholinergic binding in rat brain. Proc Natl Acad Sci USA 71: 1725–1729

    Article  Google Scholar 

  • Zhao MM, Hwa J, Perez DM (1996) Identification of critical extracellular loop residues involved in alpha 1-adrenergic receptor subtype-selective antagonist binding. Mol Pharmacol 50: 1118–1126

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Medical Centre, CMBI, NCMLS, Radboud University Nijmegen, Nijmegen, The Netherlands

    Bas Vroling, Robert P. Bywater, Laerte Oliveira & Gert Vriend

Authors
  1. Bas Vroling
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Robert P. Bywater
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Laerte Oliveira
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Gert Vriend
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

Copyright information

© 2010 Springer-Verlag/Wien

About this chapter

Cite this chapter

Vroling, B., Bywater, R.P., Oliveira, L., Vriend, G. (2010). GPCRs: Past, present, and future. In: Structural Bioinformatics of Membrane Proteins. Springer, Vienna. https://doi.org/10.1007/978-3-7091-0045-5_14

Download citation

  • DOI: https://doi.org/10.1007/978-3-7091-0045-5_14

  • Publisher Name: Springer, Vienna

  • Print ISBN: 978-3-7091-0044-8

  • Online ISBN: 978-3-7091-0045-5

  • eBook Packages: Computer ScienceComputer Science (R0)

Publish with us

Policies and ethics

Search

Navigation