Skip to main content
SpringerLink
Log in

GPCR: G protein complexes—the fundamental signaling assembly

  • Invited Review
  • Published:
Amino Acids Aims and scope Submit manuscript

Abstract

G protein coupled receptors (GPCR) constitute the largest group of cell surface receptors that transmit various signals across biological membranes through the binding and activation of heterotrimeric G proteins, which amplify the signal and activate downstream effectors leading to the biological responses. Thus, the first critical step in this signaling cascade is the interaction between receptor and its cognate G protein. Understanding this critical event at the molecular level is of high importance because abnormal function of GPCRs is associated with many diseases. Thus, these receptors are targets for drug development.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4

Similar content being viewed by others

References

  • Abdulaev NG, Ngo T, Ramon E, Brabazon DM, Marino JP, Ridge KD (2006) The receptor-bound “empty pocket” state of the heterotrimeric G-protein alpha-subunit is conformationally dynamic. Biochemistry 45(43):12986–12997. doi:10.1021/bi061088h

    Article  PubMed  CAS  Google Scholar 

  • Albizu L, Cottet M, Kralikova M, Stoev S, Seyer R, Brabet I, Roux T, Bazin H, Bourrier E, Lamarque L, Breton C, Rives ML, Newman A, Javitch J, Trinquet E, Manning M, Pin JP, Mouillac B, Durroux T (2010) Time-resolved FRET between GPCR ligands reveals oligomers in native tissues. Nat Chem Biol 6(8):587–594. doi:10.1038/nchembio.396

    Article  PubMed  CAS  Google Scholar 

  • Angel TE, Gupta S, Jastrzebska B, Palczewski K, Chance MR (2009) Structural waters define a functional channel mediating activation of the GPCR, rhodopsin. Proc Natl Acad Sci USA 106(34):14367–14372. doi:10.1073/pnas.0901074106

    Article  PubMed  CAS  Google Scholar 

  • Audet M, Bouvier M (2012) Restructuring G-protein- coupled receptor activation. Cell 151(1):14–23. doi:10.1016/j.cell.2012.09.003

    Article  PubMed  CAS  Google Scholar 

  • Baneres 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(4):815–829

    Article  PubMed  CAS  Google Scholar 

  • 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(20):14875–14881. doi:10.1074/jbc.M701433200

    Article  PubMed  CAS  Google Scholar 

  • Baylor DA, Lamb TD, Yau KW (1979) Responses of retinal rods to single photons. J Physiol 288:613–634

    PubMed  CAS  Google Scholar 

  • Cai K, Itoh Y, Khorana HG (2001) Mapping of contact sites in complex formation between transducin and light-activated rhodopsin by covalent crosslinking: use of a photoactivatable reagent. Proc Natl Acad Sci USA 98(9):4877–4882. doi:10.1073/pnas.051632898

    Article  PubMed  CAS  Google Scholar 

  • Cangiano L, Dell’Orco D (2013) Detecting single photons: a supramolecular matter? FEBS Lett 587(1):1–4. doi:10.1016/j.febslet.2012.11.015

    Article  PubMed  CAS  Google Scholar 

  • Cherezov V, Rosenbaum DM, Hanson MA, Rasmussen SG, Thian FS, Kobilka TS, Choi HJ, 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(5854):1258–1265. doi:10.1126/science.1150577

    Article  PubMed  CAS  Google Scholar 

  • Choe HW, Kim YJ, Park JH, Morizumi T, Pai EF, Krauss N, Hofmann KP, Scheerer P, Ernst OP (2011) Crystal structure of metarhodopsin II. Nature 471(7340):651–655. doi:10.1038/nature09789

    Article  PubMed  CAS  Google Scholar 

  • Chung KY, Rasmussen SG, Liu T, Li S, DeVree BT, Chae PS, Calinski D, Kobilka BK, Woods VL Jr, Sunahara RK (2011) Conformational changes in the G protein Gs induced by the beta2 adrenergic receptor. Nature 477(7366):611–615. doi:10.1038/nature10488

    Article  PubMed  CAS  Google Scholar 

  • Damian M, Martin A, Mesnier D, Pin JP, Baneres JL (2006) Asymmetric conformational changes in a GPCR dimer controlled by G-proteins. EMBO J 25(24):5693–5702. doi:10.1038/sj.emboj.7601449

    Article  PubMed  CAS  Google Scholar 

  • Dell’Orco D, Schmidt H (2008) Mesoscopic Monte Carlo simulations of stochastic encounters between photoactivated rhodopsin and transducin in disc membranes. J Phys Chem B 112(14):4419–4426. doi:10.1021/jp709963f

    Article  PubMed  Google Scholar 

  • Dell’Orco D, Schmidt H, Mariani S, Fanelli F (2009) Network-level analysis of light adaptation in rod cells under normal and altered conditions. Mol BioSyst 5(10):1232–1246. doi:10.1039/b908123b

    Article  PubMed  Google Scholar 

  • Deupi X, Edwards P, Singhal A, Nickle B, Oprian D, Schertler G, Standfuss J (2012) Stabilized G protein binding site in the structure of constitutively active metarhodopsin-II. Proc Natl Acad Sci USA 109(1):119–124. doi:10.1073/pnas.1114089108

    Article  PubMed  CAS  Google Scholar 

  • El Moustaine D, Granier S, Doumazane E, Scholler P, Rahmeh R, Bron P, Mouillac B, Baneres JL, Rondard P, Pin JP (2012) Distinct roles of metabotropic glutamate receptor dimerization in agonist activation and G-protein coupling. Proc Natl Acad Sci USA 109(40):16342–16347. doi:10.1073/pnas.1205838109

    Article  PubMed  Google Scholar 

  • Ernst OP, Gramse V, Kolbe M, Hofmann KP, Heck M (2007) Monomeric G protein-coupled receptor rhodopsin in solution activates its G protein transducin at the diffusion limit. Proc Natl Acad Sci USA 104(26):10859–10864. doi:10.1073/pnas.0701967104

    Article  PubMed  CAS  Google Scholar 

  • Farrar GJ, Millington-Ward S, Chadderton N, Humphries P, Kenna PF (2011) Gene-based therapies for dominantly inherited retinopathies. Gene Ther. doi:10.1038/gt.2011.172

    PubMed  Google Scholar 

  • 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(6):628–638

    Article  PubMed  CAS  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(6919):127–128. doi:10.1038/421127a

    Article  PubMed  CAS  Google Scholar 

  • Fotiadis D, Liang Y, Filipek S, Saperstein DA, Engel A, Palczewski K (2004) The G protein-coupled receptor rhodopsin in the native membrane. FEBS Lett 564(3):281–288

    Article  PubMed  CAS  Google Scholar 

  • Fung JJ, Deupi X, Pardo L, Yao XJ, Velez-Ruiz GA, Devree BT, Sunahara RK, Kobilka BK (2009) Ligand-regulated oligomerization of beta(2)-adrenoceptors in a model lipid bilayer. EMBO J 28(21):3315–3328. doi:10.1038/emboj.2009.267

    Article  PubMed  CAS  Google Scholar 

  • Gales C, Van Durm JJ, Schaak S, Pontier S, Percherancier Y, Audet M, Paris H, Bouvier M (2006) Probing the activation-promoted structural rearrangements in preassembled receptor-G protein complexes. Nat Struct Mol Biol 13(9):778–786. doi:10.1038/nsmb1134

    Article  PubMed  CAS  Google Scholar 

  • Govardovskii VI, Korenyak DA, Shukolyukov SA, Zueva LV (2009) Lateral diffusion of rhodopsin in photoreceptor membrane: a reappraisal. Mole Vis 15:1717–1729

    Google Scholar 

  • Gurevich VV, Gurevich EV (2008a) GPCR monomers and oligomers: it takes all kinds. Trends Neurosci 31(2):74–81. doi:10.1016/j.tins.2007.11.007

    Article  PubMed  CAS  Google Scholar 

  • Gurevich VV, Gurevich EV (2008b) How and why do GPCRs dimerize? Trends Pharmacol Sci 29(5):234–240. doi:10.1016/j.tips.2008.02.004

    Article  PubMed  CAS  Google Scholar 

  • Han M, Gurevich VV, Vishnivetskiy SA, Sigler PB, Schubert C (2001) Crystal structure of beta-arrestin at 1.9 A: possible mechanism of receptor binding and membrane translocation. Structure 9(9):869–880

    Article  PubMed  CAS  Google Scholar 

  • 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(9):688–695. doi:10.1038/nchembio.199

    Article  PubMed  CAS  Google Scholar 

  • Heck M, Schadel SA, Maretzki D, Hofmann KP (2003) Secondary binding sites of retinoids in opsin: characterization and role in regeneration. Vis Res 43(28):3003–3010

    Article  PubMed  CAS  Google Scholar 

  • Hern JA, Baig AH, Mashanov GI, Birdsall B, Corrie JE, Lazareno S, Molloy JE, Birdsall NJ (2010) Formation and dissociation of M1 muscarinic receptor dimers seen by total internal reflection fluorescence imaging of single molecules. Proc Natl Acad Sci USA 107(6):2693–2698. doi:10.1073/pnas.0907915107

    Article  PubMed  CAS  Google Scholar 

  • Hirsch JA, Schubert C, Gurevich VV, Sigler PB (1999) The 2.8 A crystal structure of visual arrestin: a model for arrestin’s regulation. Cell 97(2):257–269

    Article  PubMed  CAS  Google Scholar 

  • Huang J, Chen S, Zhang JJ, Huang XY (2013) Crystal structure of oligomeric beta1-adrenergic G protein-coupled receptors in ligand-free basal state. Nat Struct Mol Biol 20(4):419–425. doi:10.1038/nsmb.2504

    Article  PubMed  CAS  Google Scholar 

  • Huttenrauch F, Pollok-Kopp B, Oppermann M (2005) G protein-coupled receptor kinases promote phosphorylation and beta-arrestin-mediated internalization of CCR5 homo- and hetero-oligomers. J Biol Chem 280(45):37503–37515. doi:10.1074/jbc.M500535200

    Article  PubMed  Google Scholar 

  • Ianoul A, Grant DD, Rouleau Y, Bani-Yaghoub M, Johnston LJ, Pezacki JP (2005) Imaging nanometer domains of beta-adrenergic receptor complexes on the surface of cardiac myocytes. Nat Chem Biol 1(4):196–202. doi:10.1038/nchembio726

    Article  PubMed  CAS  Google Scholar 

  • Ilien B, Glasser N, Clamme JP, Didier P, Piemont E, Chinnappan R, Daval SB, Galzi JL, Mely Y (2009) Pirenzepine promotes the dimerization of muscarinic M1 receptors through a three-step binding process. J Biol Chem 284(29):19533–19543. doi:10.1074/jbc.M109.017145

    Article  PubMed  CAS  Google Scholar 

  • Itoh Y, Cai K, Khorana HG (2001) Mapping of contact sites in complex formation between light-activated rhodopsin and transducin by covalent crosslinking: use of a chemically preactivated reagent. Proc Natl Acad Sci USA 98(9):4883–4887. doi:10.1073/pnas.051632998

    Article  PubMed  CAS  Google Scholar 

  • Jastrzebska B, Fotiadis D, Jang GF, Stenkamp RE, Engel A, Palczewski K (2006) Functional and structural characterization of rhodopsin oligomers. J Biol Chem 281(17):11917–11922. doi:10.1074/jbc.M600422200

    Article  PubMed  CAS  Google Scholar 

  • Jastrzebska B, Ringler P, Lodowski DT, Moiseenkova-Bell V, Golczak M, Muller SA, Palczewski K, Engel A (2011) Rhodopsin-transducin heteropentamer: three-dimensional structure and biochemical characterization. J Struct Biol 176(3):387–394. doi:10.1016/j.jsb.2011.08.016

    Article  PubMed  CAS  Google Scholar 

  • Jastrzebska B, Orban T, Golczak M, Engel A, Palczewski K (2013a) Asymmetry of the rhodopsin dimer in complex with transducin. FASEB J. doi:10.1096/fj.12-225383

    PubMed  Google Scholar 

  • Jastrzebska B, Ringler P, Palczewski K, Engel A (2013b) The rhodopsin-transducin complex houses two distinct rhodopsin molecules. J Struct Biol. doi:10.1016/j.jsb.2013.02.014

    PubMed  Google Scholar 

  • Kisselev OG, Downs MA (2006) Rhodopsin-interacting surface of the transducin gamma subunit. Biochemistry 45(31):9386–9392. doi:10.1021/bi060806x

    Article  PubMed  CAS  Google Scholar 

  • Kobayashi H, Ogawa K, Yao R, Lichtarge O, Bouvier M (2009) Functional rescue of beta-adrenoceptor dimerization and trafficking by pharmacological chaperones. Traffic 10(8):1019–1033. doi:10.1111/j.1600-0854.2009.00932.x

    Article  PubMed  CAS  Google Scholar 

  • Lambert NA (2010) GPCR dimers fall apart. Sci Signal 3(115):pe12. doi:10.1126/scisignal.3115pe12

    Article  Google Scholar 

  • Lambright DG, Sondek J, Bohm A, Skiba NP, Hamm HE, Sigler PB (1996) The 2.0 A crystal structure of a heterotrimeric G protein. Nature 379(6563):311–319. doi:10.1038/379311a0

    Article  PubMed  CAS  Google Scholar 

  • Lebon G, Warne T, Edwards PC, Bennett K, Langmead CJ, Leslie AG, Tate CG (2011) Agonist-bound adenosine A2A receptor structures reveal common features of GPCR activation. Nature 474(7352):521–525. doi:10.1038/nature10136

    Article  PubMed  CAS  Google Scholar 

  • Liang Y, Fotiadis D, Filipek S, Saperstein DA, Palczewski K, Engel A (2003) Organization of the G protein-coupled receptors rhodopsin and opsin in native membranes. J Biol Chem 278(24):21655–21662. doi:10.1074/jbc.M302536200

    Article  PubMed  CAS  Google Scholar 

  • Manglik A, Kruse AC, Kobilka TS, Thian FS, Mathiesen JM, Sunahara RK, Pardo L, Weis WI, Kobilka BK, Granier S (2012) Crystal structure of the micro-opioid receptor bound to a morphinan antagonist. Nature 485(7398):321–326. doi:10.1038/nature10954

    Article  PubMed  CAS  Google Scholar 

  • McAlear SD, Kraft TW, Gross AK (2010) 1 rhodopsin mutations in congenital night blindness. Adv Exp Med Biol 664:263–272. doi:10.1007/978-1-4419-1399-9_30

    Article  PubMed  CAS  Google Scholar 

  • Milligan G (2010) The role of dimerisation in the cellular trafficking of G-protein-coupled receptors. Curr Opin Pharmacol 10(1):23–29. doi:10.1016/j.coph.2009.09.010

    Article  PubMed  CAS  Google Scholar 

  • Modzelewska A, Filipek S, Palczewski K, Park PS (2006) Arrestin interaction with rhodopsin: conceptual models. Cell Biochem Biophys 46(1):1–15

    Article  PubMed  CAS  Google Scholar 

  • Moepps B, Nuesseler E, Braun M, Gierschik P (2006) A homolog of the human chemokine receptor CXCR1 is expressed in the mouse. Mol Immunol 43(7):897–914. doi:10.1016/j.molimm.2005.06.043

    Article  PubMed  CAS  Google Scholar 

  • Neri M, Vanni S, Tavernelli I, Rothlisberger U (2010) Role of aggregation in rhodopsin signal transduction. Biochemistry 49(23):4827–4832. doi:10.1021/bi100478j

    Article  PubMed  CAS  Google Scholar 

  • Noel JP, Hamm HE, Sigler PB (1993) The 2.2 A crystal structure of transducin-alpha complexed with GTP gamma S. Nature 366(6456):654–663. doi:10.1038/366654a0

    Article  PubMed  CAS  Google Scholar 

  • Oldham WM, Van Eps N, Preininger AM, Hubbell WL, Hamm HE (2006) Mechanism of the receptor-catalyzed activation of heterotrimeric G proteins. Nat Struct Mol Biol 13(9):772–777. doi:10.1038/nsmb1129

    Article  PubMed  CAS  Google Scholar 

  • Orban T, Jastrzebska B, Gupta S, Wang B, Miyagi M, Chance MR, Palczewski K (2012) Conformational dynamics of activation for the pentameric complex of dimeric G protein-coupled receptor and heterotrimeric G protein. Structure 20(5):826–840. doi:10.1016/j.str.2012.03.017

    Article  PubMed  CAS  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(5480):739–745

    Article  PubMed  CAS  Google Scholar 

  • Park JH, Scheerer P, Hofmann KP, Choe HW, Ernst OP (2008) Crystal structure of the ligand-free G-protein-coupled receptor opsin. Nature 454(7201):183–187. doi:10.1038/nature07063

    Article  PubMed  CAS  Google Scholar 

  • Pellissier LP, Barthet G, Gaven F, Cassier E, Trinquet E, Pin JP, Marin P, Dumuis A, Bockaert J, Baneres 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(12):9985–9997. doi:10.1074/jbc.M110.201939

    Article  PubMed  CAS  Google Scholar 

  • Pescitelli G, Sreerama N, Salvadori P, Nakanishi K, Berova N, Woody RW (2008) Inherent chirality dominates the visible/near-ultraviolet CD spectrum of rhodopsin. J Am Chem Soc 130(19):6170–6181. doi:10.1021/ja711009y

    Article  PubMed  CAS  Google Scholar 

  • Rasmussen SG, Choi HJ, Rosenbaum DM, Kobilka TS, Thian FS, Edwards PC, Burghammer M, Ratnala VR, Sanishvili R, Fischetti RF, Schertler GF, Weis WI, Kobilka BK (2007) Crystal structure of the human beta2 adrenergic G-protein-coupled receptor. Nature 450(7168):383–387. doi:10.1038/nature06325

    Article  PubMed  CAS  Google Scholar 

  • Rasmussen SG, Choi HJ, Fung JJ, Pardon E, Casarosa P, Chae PS, Devree BT, Rosenbaum DM, Thian FS, Kobilka TS, Schnapp A, Konetzki I, Sunahara RK, Gellman SH, Pautsch A, Steyaert J, Weis WI, Kobilka BK (2011a) Structure of a nanobody-stabilized active state of the beta(2) adrenoceptor. Nature 469(7329):175–180. doi:10.1038/nature09648

    Article  PubMed  CAS  Google Scholar 

  • 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 (2011b) Crystal structure of the beta2 adrenergic receptor-Gs protein complex. Nature 477(7366):549–555. doi:10.1038/nature10361

    Article  PubMed  CAS  Google Scholar 

  • Rivero-Muller 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 USA 107(5):2319–2324. doi:10.1073/pnas.0906695106

    Article  PubMed  CAS  Google Scholar 

  • Ruprecht JJ, Mielke T, Vogel R, Villa C, Schertler GF (2004) Electron crystallography reveals the structure of metarhodopsin I. EMBO J 23(18):3609–3620. doi:10.1038/sj.emboj.7600374

    Article  PubMed  CAS  Google Scholar 

  • Salahpour A, Angers S, Mercier JF, Lagace M, Marullo S, Bouvier M (2004) Homodimerization of the beta2-adrenergic receptor as a prerequisite for cell surface targeting. J Biol Chem 279(32):33390–33397. doi:10.1074/jbc.M403363200

    Article  PubMed  CAS  Google Scholar 

  • Salom D, Lodowski DT, Stenkamp RE, Le Trong I, Golczak M, Jastrzebska B, Harris T, Ballesteros JA, Palczewski K (2006) Crystal structure of a photoactivated deprotonated intermediate of rhodopsin. Proc Natl Acad Sci USA 103(44):16123–16128. doi:10.1073/pnas.0608022103

    Article  PubMed  CAS  Google Scholar 

  • Scheerer P, Park JH, Hildebrand PW, Kim YJ, Krauss N, Choe HW, Hofmann KP, Ernst OP (2008) Crystal structure of opsin in its G-protein-interacting conformation. Nature 455(7212):497–502. doi:10.1038/nature07330

    Article  PubMed  CAS  Google Scholar 

  • Schertler GF, Hargrave PA (1995) Projection structure of frog rhodopsin in two crystal forms. Proc Natl Acad Sci USA 92(25):11578–11582

    Article  PubMed  CAS  Google Scholar 

  • Schertler GF, Villa C, Henderson R (1993) Projection structure of rhodopsin. Nature 362(6422):770–772. doi:10.1038/362770a0

    Article  PubMed  CAS  Google Scholar 

  • Shi GW, Chen J, Concepcion F, Motamedchaboki K, Marjoram P, Langen R (2005) Light causes phosphorylation of nonactivated visual pigments in intact mouse rod photoreceptor cells. J Biol Chem 280(50):41184–41191. doi:10.1074/jbc.M506935200

    Article  PubMed  CAS  Google Scholar 

  • Sommer ME, Hofmann KP, Heck M (2012) Distinct loops in arrestin differentially regulate ligand binding within the GPCR opsin. Nature Commun 3:995. doi:10.1038/ncomms2000

    Article  Google Scholar 

  • Sondek J, Bohm A, Lambright DG, Hamm HE, Sigler PB (1996) Crystal structure of a G-protein beta gamma dimer at 2.1A resolution. Nature 379(6563):369–374. doi:10.1038/379369a0

    Article  PubMed  CAS  Google Scholar 

  • Standfuss J, Xie G, Edwards PC, Burghammer M, Oprian DD, Schertler GF (2007) Crystal structure of a thermally stable rhodopsin mutant. J Mol Biol 372(5):1179–1188. doi:10.1016/j.jmb.2007.03.007

    Article  PubMed  CAS  Google Scholar 

  • Struts AV, Salgado GF, Brown MF (2011) Solid-state 2H NMR relaxation illuminates functional dynamics of retinal cofactor in membrane activation of rhodopsin. Proc Natl Acad Sci USA 108(20):8263–8268. doi:10.1073/pnas.1014692108

    Article  PubMed  CAS  Google Scholar 

  • Sutton RB, Vishnivetskiy SA, Robert J, Hanson SM, Raman D, Knox BE, Kono M, Navarro J, Gurevich VV (2005) Crystal structure of cone arrestin at 2.3A: evolution of receptor specificity. J Mol Biol 354(5):1069–1080. doi:10.1016/j.jmb.2005.10.023

    Article  PubMed  CAS  Google Scholar 

  • Tanaka T, Nomura W, Narumi T, Masuda A, Tamamura H (2010) Bivalent ligands of CXCR4 with rigid linkers for elucidation of the dimerization state in cells. J Am Chem Soc 132(45):15899–15901. doi:10.1021/ja107447w

    Article  PubMed  CAS  Google Scholar 

  • Van Eps N, Oldham WM, Hamm HE, Hubbell WL (2006) Structural and dynamical changes in an alpha-subunit of a heterotrimeric G protein along the activation pathway. Proc Natl Acad Sci USA 103(44):16194–16199. doi:10.1073/pnas.0607972103

    Article  PubMed  Google Scholar 

  • Van Eps N, Preininger AM, Alexander N, Kaya AI, Meier S, Meiler J, Hamm HE, Hubbell WL (2011) Interaction of a G protein with an activated receptor opens the interdomain interface in the alpha subunit. Proc Natl Acad Sci USA 108(23):9420–9424. doi:10.1073/pnas.1105810108

    Article  PubMed  Google Scholar 

  • 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(2):126–131. doi:10.1038/nchembio.64

    Article  PubMed  CAS  Google Scholar 

  • Vobornik D, Rouleau Y, Haley J, Bani-Yaghoub M, Taylor R, Johnston LJ, Pezacki JP (2009) Nanoscale organization of beta2-adrenergic receptor-Venus fusion protein domains on the surface of mammalian cells. Biochem Biophys Res Commun 382(1):85–90. doi:10.1016/j.bbrc.2009.02.144

    Article  PubMed  CAS  Google Scholar 

  • Wen Y, Locke KG, Hood DC, Birch DG (2011) Rod photoreceptor temporal properties in retinitis pigmentosa. Exp Eye Res 92(3):202–208. doi:10.1016/j.exer.2010.12.014

    Article  PubMed  CAS  Google Scholar 

  • Wettschureck N, Offermanns S (2005) Mammalian G proteins and their cell type specific functions. Physiol Rev 85(4):1159–1204. doi:10.1152/physrev.00003.2005

    Article  PubMed  CAS  Google Scholar 

  • White JF, Noinaj N, Shibata Y, Love J, Kloss B, Xu F, Gvozdenovic-Jeremic J, Shah P, Shiloach J, Tate CG, Grisshammer R (2012) Structure of the agonist-bound neurotensin receptor. Nature 490(7421):508–513. doi:10.1038/nature11558

    Article  PubMed  CAS  Google Scholar 

  • 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 USA 104(18):7682–7687. doi:10.1073/pnas.0611448104

    Article  PubMed  CAS  Google Scholar 

  • Whorton MR, Jastrzebska B, Park PS, Fotiadis D, Engel A, Palczewski K, Sunahara RK (2008) Efficient coupling of transducin to monomeric rhodopsin in a phospholipid bilayer. J Biol Chem 283(7):4387–4394. doi:10.1074/jbc.M703346200

    Article  PubMed  CAS  Google Scholar 

  • Wu B, Chien EY, Mol CD, Fenalti G, Liu W, Katritch V, Abagyan R, Brooun A, Wells P, Bi FC, Hamel DJ, Kuhn P, Handel TM, Cherezov V, Stevens RC (2010) Structures of the CXCR4 chemokine GPCR with small-molecule and cyclic peptide antagonists. Science 330(6007):1066–1071. doi:10.1126/science.1194396

    Article  PubMed  CAS  Google Scholar 

  • Wu H, Wacker D, Mileni M, Katritch V, Han GW, Vardy E, Liu W, Thompson AA, Huang XP, Carroll FI, Mascarella SW, Westkaemper RB, Mosier PD, Roth BL, Cherezov V, Stevens RC (2012) Structure of the human kappa-opioid receptor in complex with JDTic. Nature 485(7398):327–332. doi:10.1038/nature10939

    Article  PubMed  CAS  Google Scholar 

  • Xu F, Wu H, Katritch V, Han GW, Jacobson KA, Gao ZG, Cherezov V, Stevens RC (2011) Structure of an agonist-bound human A2A adenosine receptor. Science 332(6027):322–327. doi:10.1126/science.1202793

    Article  PubMed  CAS  Google Scholar 

Download references

Acknowledgments

I thank Drs. Krzysztof Palczewski and Leslie T. Webster, Jr. (Case Western Reserve University) for valuable comments on the manuscript. This work was supported in part by NIH Grants R01-EY0008061, and R01 GM079191.

Conflict of interest

The author declares that she has no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Pharmacology, School of Medicine, Case Western Reserve University, 10900 Euclid Ave, Cleveland, OH, 44106-4965, USA

    Beata Jastrzebska

Authors
  1. Beata Jastrzebska
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Beata Jastrzebska.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Jastrzebska, B. GPCR: G protein complexes—the fundamental signaling assembly. Amino Acids 45, 1303–1314 (2013). https://doi.org/10.1007/s00726-013-1593-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00726-013-1593-y

Keywords

Search

Navigation