Receptor-mediated activation of heterotrimeric G-proteins: Current structural insights

Molecular Pharmacology

Volumn 72, Issue 2, 2007, Pages 219-230

  Johnston, Christopher A ^a   Siderovski, David P ^a  

^a UNIVERSITY OF NORTH CAROLINA SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

G PROTEIN COUPLED RECEPTOR; GUANINE NUCLEOTIDE BINDING PROTEIN; GUANOSINE DIPHOSPHATE; GUANOSINE TRIPHOSPHATE; RHODOPSIN;

ALPHA CHAIN; CARBOXY TERMINAL SEQUENCE; DIMERIZATION; MOLECULAR INTERACTION; PRIORITY JOURNAL; PROTEIN STRUCTURE; RECEPTOR INTRINSIC ACTIVITY; SHORT SURVEY; SIGNAL TRANSDUCTION;

AMINO ACID SEQUENCE; ANIMALS; DIMERIZATION; HETEROTRIMERIC GTP-BINDING PROTEINS; HUMANS; MODELS, MOLECULAR; MOLECULAR SEQUENCE DATA; RECEPTORS, G-PROTEIN-COUPLED; RHODOPSIN; SIGNAL TRANSDUCTION;

EID: 34547157646     PISSN: 0026895X     EISSN: 15210111     Source Type: Journal    
DOI: 10.1124/mol.107.034348     Document Type: Short Survey

References (109)

1. Abdulaev NG, Ngo T, Ramon E, Brabazon DM, Marino JP, and Ridge KD (2006) The receptor-bound "empty pocket" state of the heterotrimeric G-protein alpha-subunit is conformationally dynamic. Biochemistry 45:12986-12997.
2. Altenbach C, Cai K, Klein-Seetharaman J, Khorana HG, and Hubbell WL (2001) Structure and function in rhodopsin: mapping light-dependent changes in distance between residue 65 in helix TM1 and residues in the sequence 306-319 at the cytoplasmic end of helix TM7 and in helix H8. Biochemistry 40:15483-15492.
3. Angers S, Salahpour A, and Bouvier M (2002) Dimerization: an emerging concept for G protein-coupled receptor ontogeny and function. Annu Rev Pharmacol Toxicol 42:409-435.
4. Ballesteros JA, Jensen AD, Liapakis G, Rasmussen SG, Shi L, Gether U, and Javitch JA (2001) Activation of the β2-adrenergic receptor involves disruption of an ionic lock between the cytoplasmic ends of transmembrane segments 3 and 6. J Biol Chem 276:29171-29177.
5. Berman DM, Kozasa T, and Gilman AG (1996) The GTPase-activating protein RGS4 stabilizes the transition state for nucleotide hydrolysis. J Biol Chem 271:27209-27212.
6. Bohm A, Gaudet R, and Sigler PB (1997) Structural aspects of heterotrimeric G-protein signaling. Curr Opin Biotechnol 8:480-487.
7. Bourne HR (1997) How receptors talk to trimeric G proteins. Curr Opin Cell Biol 9:134-142.
8. Chabre M and le Maire M (2005) Monomeric G-protein-coupled receptor as a functional unit. Biochemistry 44:9395-9403.
9. Chen Z, Singer WD, Sternweis PC, and Sprang SR (2005) Structure of the p115RhoGEF rgRGS domain-Galpha13/i1 chimera complex suggests convergent evolution of a GTPase activator. Nat Struct Mol Biol 12:191-197.
10. Cherfils J and Chabre M (2003) Activation of G-protein Galpha subunits by receptors through Galpha-Gbeta and Galpha-Ggamma interactions. Trends Biochem Sci 28:13-17.
11. Cherfils J and Chardin P (1999) GEFs: structural basis for their activation of small GTP-binding proteins. Trends Biochem Sci 24:306-311.
12. Coleman DE, Berghuis AM, Lee E, Linder ME, Gilman AG, and Sprang SR (1994) Structures of active conformations of Gi alpha 1 and the mechanism of GTP hydrolysis. Science 265:1405-1412.
13. α protein-substrate complex. J Biol Chem 274:16669-16672.
14. Davis TL, Bonacci TM, Sprang SR, and Smrcka AV (2005) Structural and molecular characterization of a preferred protein interaction surface on G protein beta gamma subunits. Biochemistry 44:10593-10604.
15. Ferguson KM, Higashijima T, Smigel MD, and Gilman AG (1986) The influence of bound GDP on the kinetics of guanine nucleotide binding to G proteins. J Biol Chem 261:7393-7399.
16. Flanagan CA (2005) A GPCR that is not "DRY". Mol Pharmacol 68:1-3.
17. Ford CE, Skiba NP, Bae H, Daaka Y, Reuveny E, Shekter LR, Rosal R, Weng G, Yang CS, Iyengar R, et al. (1998) Molecular basis for interactions of G protein beta-gamma subunits with effectors. Science 280:1271-1274.
18. Fotiadis D, Jastrzebska B, Philippsen A, Muller DJ, Palczewski K, and Engel A (2006) Structure of the rhodopsin dimer: a working model for G-protein-coupled receptors. Curr Opin Struct Biol 16:252-259.
19. Fredriksson R, Lagerstrom MC, Lundin LG, and Schioth HB (2003) The G-protein-coupled receptors in the human genome form five main families. Phylogenetic analysis, paralogon groups, and fingerprints. Mol Pharmacol 63:1256-1272.
20. Fung BK (1983) Characterization of transducin from bovine retinal rod outer segments. I. Separation and reconstitution of the subunits. J Biol Chem 258:10495-10502.
21. Fung BK and Nash CR (1983) Characterization of transducin from bovine retinal rod outer segments. II. Evidence for distinct binding sites and conformational changes revealed by limited proteolysis with trypsin. J Biol Chem 258:10503-10510.
22. Gaudet R, Bohm A, and Sigler PB (1996) Crystal structure at 2.4 angstroms resolution of the complex of transducin betagamma and its regulator, phosducin. Cell 87:577-588.
23. Ghanouni P, Steenhuis JJ, Farrens DL, and Kobilka BK (2001) Agonist-induced conformational changes in the G-protein-coupling domain of the beta 2 adrenergic receptor. Proc Natl Acad Sci U S A 98:5997-6002.
24. Gilman AG (1987) G proteins: transducers of receptor-generated signals. Annu Rev Biochem 56:615-649.
25. Grishina G and Berlot CH (2000) A surface-exposed region of G(salpha) in which substitutions decrease receptor-mediated activation and increase receptor affinity. Mol Pharmacol 57:1081-1092.
26. Hamm HE (1998) The many faces of G protein signaling. J Biol Chem 273:669-672.
27. Hamm HE, Deretic D, Arendt A, Hargrave PA, Koenig B, and Hofmann KP (1988) Site of G protein binding to rhodopsin mapped with synthetic peptides from the alpha subunit. Science 241:832-835.
28. 2+ and the βγ-subunit complex on the interactions of guanine nucleotides with G proteins. J Biol Chem 262:762-766.
29. Higgins JB and Casey PJ (1994) In vitro processing of recombinant G protein gamma subunits. Requirements for assembly of an active βγ complex. J Biol Chem 269:9067-9073.
30. Hou Y, Azpiazu I, Smrcka A, and Gautam N (2000) Selective role of G protein gamma subunits in receptor interaction. J Biol Chem 275:38961-38964.
31. Hou Y, Chang V, Capper AB, Taussig R, and Gautam N (2001) G Protein beta subunit types differentially interact with a muscarinic receptor but not adenylyl cyclase type II or phospholipase C-β 2/3. J Biol Chem 276:19982-19988.
32. Iiri T, Farfel Z, and Bourne HR (1998) G-protein diseases furnish a model for the turn-on switch. Nature 394:35-38.
33. Iiri T, Herzmark P, Nakamoto JM, van Dop C, and Bourne HR (1994) Rapid GDP release from Gs alpha in patients with gain and loss of endocrine function. Nature 371:164-168.
34. Iñiguez-Lluhi JA, Simon MI, Robishaw JD, and Gilman AG (1992) G protein beta gamma subunits synthesized in Sf9 cells. Functional characterization and the significance of prenylation of gamma. J Biol Chem 267:23409-23417.
35. sα mutants with decreased ability to activate adenylylcyclase. J Biol Chem 266:16226-16231.
36. Johnston CA, Lobanova ES, Shavkunov AS, Low J, Ramer JK, Blaesius R, Fredericks Z, Willard FS, Kuhlman B, Arshavsky VY, et al. (2006) Minimal determinants for binding activated G alpha from the structure of a G alpha(i1)-peptide dimer. Biochemistry 45:11390-11400.
37. Johnston CA and Siderovski DP (2007) A structural basis for nucleotide exchange on G-alpha-i subunits and receptor coupling specificity. Proc Natl Acad Sci U S A 104:2001-2006.
38. Johnston CA, Willard FS, Jezyk MR, Fredericks Z, Bodor ET, Jones MB, Blaesius R, Watts VJ, Harden TK, Sondek J, et al. (2005) Structure of Galpha(i1) bound to a GDP-selective peptide provides insight into guanine nucleotide exchange. Structure 13:1069-1080.
39. Karasinska JM, George SR, and O'Dowd BF (2003) Family 1 G protein-coupled receptor function in the CNS. Insights from gene knockout mice. Brain Res Brain Res Rev 41:125-152.
40. Kawashima T, Berthet-Colominas C, Wulff M, Cusack S, and Leberman R (1996) The structure of the Escherichia coli EF-Tu·EF-Ts complex at 2.5 A resolution. Nature 379:511-518.
41. Kenakin T (2004) Efficacy as a vector: the relative prevalence and paucity of inverse agonism. Mol Pharmacol 65:2-11.
42. Kimple RJ, Kimple ME, Betts L, Sondek J, and Siderovski DP (2002) Structural determinants for GoLoco-induced inhibition of nucleotide release by Galpha subunits. Nature 416:878-881.
43. Kisselev OG, Kao J, Ponder JW, Fann YC, Gautam N, and Marshall GR (1998) Light-activated rhodopsin induces structural binding motif in G protein alpha subunit. Proc Natl Acad Sci U S A 95:4270-4275.
44. Kisselev OG, Meyer CK, Heck M, Ernst OP, and Hofmann KP (1999) Signal transfer from rhodopsin to the G-protein: evidence for a two-site sequential fit mechanism. Proc Natl Acad Sci U S A 96:4898-4903.
45. Lambright DG, Noel JP, Hamm HE, and Sigler PB (1994) Structural determinants for activation of the alpha-subunit of a heterotrimeric G protein. Nature 369:621-628.
46. Lambright DG, Sondek J, Bohm A, Skiba NP, Hamm HE, and Sigler PB (1996) The 2.0 A crystal structure of a heterotrimeric G protein. Nature 379:311-319.
47. Li D and Roberts R (2001) WD-repeat proteins: structure characteristics, biological function, and their involvement in human diseases. Cell Mol Life Sci 58:2085-2097.
48. Lodowski DT, Pitcher JA, Capel WD, Lefkowitz RJ, and Tesmer JJ (2003) Keeping G proteins at bay: a complex between G protein-coupled receptor kinase 2 and Gbetagamma. Science 300:1256-1262.
49. Mahon MJ, Bonacci TM, Divieti P, and Smrcka AV (2006) A docking site for G protein betagamma subunits on the parathyroid hormone 1 receptor supports signaling through multiple pathways. Mol Endocrinol 20:136-146.
50. Manahan CL, Patnana M, Blumer KJ, and Linder ME (2000) Dual lipid modification motifs in G(alpha) and G(gamma) subunits are required for full activity of the pheromone response pathway in Saccharomyces cerevisiae. Mol Biol Cell 11:957-968.
51. Marin EP, Krishna AG, and Sakmar TP (2001) Rapid activation of transducin by mutations distant from the nucleotide-binding site: evidence for a mechanistic model of receptor-catalyzed nucleotide exchange by G proteins. J Biol Chem 276:27400-27405.
52. Marin EP, Krishna AG, and Sakmar TP (2002) Disruption of the alpha5 helix of transducin impairs rhodopsin-catalyzed nucleotide exchange. Biochemistry 41:6988-6994.
53. sα: evidence for intramolecular signal transduction. Mol Pharmacol 53:981-990.
54. McCudden CR, Hains MD, Kimple RJ, Siderovski DP, and Willard FS (2005) G-protein signaling: back to the future. Cell Mol Life Sci 62:551-577.
55. Mehler EL, Hassan SA, Kortagere S, and Weinstein H (2006) Ab initio computational modeling of loops in G-protein-coupled receptors: lessons from the crystal structure of rhodopsin. Proteins 64:673-690.
56. Mixon MB, Lee E, Coleman DE, Berghuis AM, Gilman AG, and Sprang SR (1995) Tertiary and quaternary structural changes in Gi alpha 1 induced by GTP hydrolysis. Science 270:954-960.
57. Muntz KH, Sternweis PC, Gilman AG, and Mumby SM (1992) Influence of gamma subunit prenylation on association of guanine nucleotide-binding regulatory proteins with membranes. Mol Biol Cell 3:49-61.
58. Nanoff C, Koppensteiner R, Yang Q, Fuerst E, Ahorn H, and Freissmuth M (2006) The carboxyl terminus of the Gα-subunit is the latch for triggered activation of heterotrimeric G proteins. Mol Pharmacol 69:397-405.
59. Natochin M, Moussaif M, and Artemyev NO (2001) Probing the mechanism of rhodopsin-catalyzed transducin activation. J Neurochem 77:202-210.
60. Neer EJ, Schmidt CJ, Nambudripad R, and Smith TF (1994) The ancient regulatory-protein family of WD-repeat proteins. Nature 371:297-300.
61. Noel JP, Hamm HE, and Sigler PB (1993) The 2.2 A crystal structure of transducinalpha complexed with GTP gamma S. Nature 366:654-663.
62. Offermanns S (2003) G-proteins as transducers in transmembrane signalling. Prog Biophys Mol Biol 83:101-130.
63. Oldham WM, Van Eps N, Preininger AM, Hubbell WL, and Hamm HE (2006) Mechanism of the receptor-catalyzed activation of heterotrimeric G proteins. Nat Struct Mol Biol 13:772-777.
64. Onrust R, Herzmark P, Chi P, Garcia PD, Lichtarge O, Kingsley C, and Bourne HR (1997) Receptor and betagamma binding sites in the alpha subunit of the retinal G protein transducin. Science 275:381-384.
65. Overington JP, Al-Lazikani B, and Hopkins AL (2006) How many drug targets are there? Nat Rev Drug Discov 5:993-996.
66. Palczewski K, Kumasaka T, Hori T, Behnke CA, Motoshima H, Fox BA, Le Trong I, Teller DC, Okada T, Stenkamp RE, et al. (2000) Crystal structure of rhodopsin: a G protein-coupled receptor. Science 289:739-745.
67. Posner BA, Mixon MB, Wall MA, Sprang SR, and Gilman AG (1998) The A326S mutant of Giα1 as an approximation of the receptor-bound state. J Biol Chem 273:21752-21758.
68. Prinster SC, Hague C, and Hall RA (2005) Heterodimerization of G protein-coupled receptors: specificity and functional significance. Pharmacol Rev 57:289-298.
69. Raw AS, Coleman DE, Gilman AG, and Sprang SR (1997) Structural and biochemical characterization of the GTPγS-, GDP·Pi-, and GDP-bound forms of a GTPase-deficient Gly42 → Val mutant of Gialpha1. Biochemistry 36:15660-15669.
70. Remmers AE, Engel C, Liu M, and Neubig RR (1999) Interdomain interactions regulate GDP release from heterotrimeric G proteins. Biochemistry 38:13795-13800.
71. Rohrer DK and Kobilka BK (1998) G protein-coupled receptors: functional and mechanistic insights through altered gene expression. Physiol Rev 78:35-52.
72. Rondard P, Iiri T, Srinivasan S, Meng E, Fujita T, and Bourne HR (2001) Mutant G protein alpha subunit activated by Gbeta gamma: a model for receptor activation? Proc Natl Acad Sci U S A 98:6150-6155.
73. Ross EM and Wilkie TM (2000) GTPase-activating proteins for heterotrimeric G proteins: regulators of G protein signaling (RGS) and RGS-like proteins. Annu Rev Biochem 69:795-827.
74. Rossman KL, Der CJ, and Sondek J (2005) GEF means go: turning on RHO GTPases with guanine nucleotide-exchange factors. Nat Rev Mol Cell Biol 6:167-180.
75. Rovati GE, Capra V, and Neubig RR (2007) The highly conserved DRY motif of class A G protein-coupled receptors: beyond the ground state. Mol Pharmacol 71:959-964.
76. Salom D, Lodowski DT, Stenkamp RE, Le Trong I, Golczak M, Jastrzebska B, Harris T, Ballesteros JA, and Palczewski K (2006) Crystal structure of a photoactivated deprotonated intermediate of rhodopsin. Proc Natl Acad Sci U S A 103:16123-16128.
77. Sarramegn V, Muller I, Milon A, and Talmont F (2006) Recombinant G protein-coupled receptors from expression to renaturation: a challenge towards structure. Cell Mol Life Sci 63:1149-1164.
78. Schmidt CJ, Thomas TC, Levine MA, and Neer EJ (1992) Specificity of G protein β and γ subunit interactions. J Biol Chem 267:13807-13810.
79. Schwartz TW and Holst B (2006) Ago-allosteric modulation and other types of allostery in dimeric 7TM receptors. J Recept Signal Transduct Res 26:107-128.
80. Siderovski DP, Hessel A, Chung S, Mak TW, and Tyers M (1996) A new family of regulators of G-protein-coupled receptors? Curr Biol 6:211-212.
81. Siderovski DP and Willard FS (2005) The GAPs, GEFs, and GDIs of heterotrimeric G-protein alpha subunits. Int J Biol Sci 1:51-66.
82. Slep KC, Kercher MA, He W, Cowan CW, Wensel TG, and Sigler PB (2001) Structural determinants for regulation of phosphodiesterase by a G protein at 2.0 A. Nature 409:1071-1077.
83. Slessareva JE, Ma H, Depree KM, Flood LA, Bae H, Cabrera-Vera TM, Hamm HE, and Graber SG (2003) Closely related G-protein-coupled receptors use multiple and distinct domains on G-protein α-subunits for selective coupling. J Biol Chem 278:50530-50536.
84. Sondek J, Bohm A, Lambright DG, Hamm HE, and Sigler PB (1996) Crystal structure of a G-protein beta gamma dimer at 2.1 Å resolution. Nature 379:369-374.
85. Sondek J, Lambright DG, Noel JP, Hamm HE, and Sigler PB (1994) GTPase mechanism of G proteins from the 1.7-Å crystal structure of transducin alpha-GDP-AIF-4. Nature 372:276-279.
86. Spiegel AM and Weinstein LS (2004) Inherited diseases involving g proteins and g protein-coupled receptors. Annu Rev Med 55:27-39.
87. Sprang SR (1997) G protein mechanisms: insights from structural analysis. Annu Rev Biochem 66:639-678.
88. Srinivasa SP, Watson N, Overton MC, and Blumer KJ (1998) Mechanism of RGS4, a GTPase-activating protein for G protein α subunits. J Biol Chem 273:1529-1533.
89. Sunahara RK, Tesmer JJ, Gilman AG, and Sprang SR (1997) Crystal structure of the adenylyl cyclase activator Gsalpha. Science 278:1943-1947.
90. Swaminath G, Deupi X, Lee TW, Zhu W, Thian FS, Kobilka TS, and Kobilka B (2005) Probing the β2 adrenoceptor binding site with catechol reveals differences in binding and activation by agonists and partial agonists. J Biol Chem 280:22165-22171.
91. Takeda S, Kadowaki S, Haga T, Takaesu H, and Mitaku S (2002) Identification of G protein-coupled receptor genes from the human genome sequence. FEBS Lett 520:97-101.
92. Taylor JM, Jacob-Mosier GG, Lawton RG, VanDort M, and Neubig RR (1996) Receptor and membrane interaction sites on Gβ. A receptor-derived peptide binds to the carboxyl terminus. J Biol Chem 271:3336-3339.
93. Tesmer JJ, Berman DM, Gilman AG, and Sprang SR (1997a) Structure of RGS4 bound to AlF4-activated G(i alpha1): stabilization of the transition state for GTP hydrolysis. Cell 89:251-261.
94. Tesmer JJ, Sunahara RK, Gilman AG, and Sprang SR (1997b) Crystal structure of the catalytic domains of adenylyl cyclase in a complex with Gsalpha.GTPgammaS. Science 278:1907-1916.
95. Tesmer VM, Kawano T, Shankaranarayanan A, Kozasa T, and Tesmer JJ (2005) Snapshot of activated G proteins at the membrane: the Galphaq-GRK2-Gbetagamma complex. Science 310:1686-1690.
96. Thomas TC, Schmidt CJ, and Neer EJ (1993) G-protein alpha o subunit: mutation of conserved cysteines identifies a subunit contact surface and alters GDP affinity. Proc Natl Acad Sci U S A 90:10295-10298.
97. Thomas TO, Bae H, Medkova M, and Hamm HE (2001) An intramolecular contact in Galpha transducin that participates in maintaining its intrinsic GDP release rate. Mol Cell Biol Res Commun 4:282-291.
98. Van Eps N, Oldham WM, Hamm HE, and Hubbell WL (2006) Structural and dynamical changes in an alpha-subunit of a heterotrimeric G protein along the activation pathway. Proc Natl Acad Sci U S A 103:16194-16199.
99. Wade SM, Scribner MK, Dalman HM, Taylor JM, and Neubig RR (1996) Structural requirements for G(o) activation by receptor-derived peptides: activation and modulation domains of the alpha 2-adrenergic receptor i3c region. Mol Pharmacol 50:351-358.
100. Waldhoer M, Fong J, Jones RM, Lunzer MM, Sharma SK, Kostenis E, Portoghese PS, and Whistler JL (2005) A heterodimer-selective agonist shows in vivo relevance of G protein-coupled receptor dimers. Proc Natl Acad Sci U S A 102:9050-9055.
101. Wall MA, Coleman DE, Lee E, Iñiguez-Lluhi JA, Posner BA, Gilman AG, and Sprang SR (1995) The structure of the G protein heterotrimer Gi alpha 1 beta 1 gamma 2. Cell 83:1047-1058.
102. Wall MA, Posner BA, and Sprang SR (1998) Structural basis of activity and subunit recognition in G protein heterotrimers. Structure 6:1169-1183.
103. Wedegaertner PB, Wilson PT, and Bourne HR (1995) Lipid modifications of trimeric G proteins. J Biol Chem 270:503-506.
104. White JH, Wise A, Main MJ, Green A, Fraser NJ, Disney GH, Barnes AA, Emson P, Foord SM, and Marshall FH (1998) Heterodimerization is required for the formation of a functional GABA(B) receptor. Nature 396:679-682.
105. Wu G, Benovic JL, Hildebrandt JD, and Lanier SM (1998) Receptor docking sites for G-protein βγ subunits. Implications for signal regulation. J Biol Chem 273:7197-7200.
106. 3-muscarinic receptor and their role in receptor regulation. J Biol Chem 275:9026-9034.
107. Yang AH, Ishii I, and Chun J (2002) In vivo roles of lysophospholipid receptors revealed by gene targeting studies in mice. Biochim Biophys Acta 1582:197-203.
108. Yang CS, Skiba NP, Mazzoni MR, and Hamm HE (1999) Conformational changes at the carboxyl terminus of Gα occur during G protein activation. J Biol Chem 274:2379-2385.
109. Zhang Y, Devries ME, and Skolnick J (2006) Structure modeling of all identified G protein-coupled receptors in the human genome. PLoS Comput Biol 2:e13.