Ligand binding and micro-switches in 7TM receptor structures

Trends in Pharmacological Sciences

Volumn 30, Issue 5, 2009, Pages 249-259

  Nygaard, Rie ^a,b   Frimurer, Thomas M ^b   Holst, Birgitte ^a   Rosenkilde, Mette M ^a   Schwartz, Thue W ^a,c  

^a UNIVERSITY OF COPENHAGEN   (Denmark)

^b 7TM Pharma ^*  (Denmark)

^c Prosidion Limited   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

4 [2 [7 AMINO 2 (2 FURYL) 1,2,4 TRIAZOLO[2,3 A][1,3,5]TRIAZIN 5 YLAMINO]ETHYL]PHENOL; ARGININE; CARAZOLOL; GUANINE NUCLEOTIDE BINDING PROTEIN; MEMBRANE PROTEIN; OPSIN; RHODOPSIN; TRANSMEMBRANE RECEPTOR; TRANSMEMBRANE RECEPTOR ANTAGONIST; UNCLASSIFIED DRUG;

ALLOSTERISM; ANIMAL CELL; CHEMICAL STRUCTURE; EXTRACELLULAR LOOP; HYDROGEN BOND; INTRACELLULAR TRANSPORT; LIGAND BINDING; MEMBRANE POTENTIAL; MEMBRANE STRUCTURE; NONHUMAN; PRIORITY JOURNAL; PROTEIN CONFORMATION; PROTEIN DOMAIN; REVIEW;

ALLOSTERIC REGULATION; BINDING SITES; DRUG AGONISM; DRUG ANTAGONISM; LIGANDS; MODELS, MOLECULAR; MOLECULAR CONFORMATION; MOLECULAR STRUCTURE; PROTEIN INTERACTION DOMAINS AND MOTIFS; RECEPTORS, G-PROTEIN-COUPLED;

EID: 65449161390     PISSN: 01656147     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.tips.2009.02.006     Document Type: Review

References (66)

1. Schertler G.F. Structure of rhodopsin and the metarhodopsin I photointermediate. Curr. Opin. Struct. Biol. 15 (2005) 408-415
2. Kobilka B., and Schertler G.F. New G-protein-coupled receptor crystal structures: insights and limitations. Trends Pharmacol. Sci. 29 (2008) 79-83
3. Hanson M.A., and Stevens R.C. Discovery of new GPCR biology: one receptor structure at a time. Structure 17 (2009) 8-14
4. Schwartz T.W., and Rosenkilde M.M. Is there a 'lock' for all 'keys' in 7TM receptors. Trends Pharmacol. Sci. 17 (1996) 213-216
5. Pierce K.L., et al. Seven-transmembrane receptors. Nat. Rev. Mol. Cell Biol. 3 (2002) 639-650
6. Hubbell W.L., et al. Rhodopsin structure, dynamics, and activation: a perspective from crystallography, site-directed spin labeling, sulfhydryl reactivity, and disulfide cross-linking. Adv. Protein Chem. 63 (2003) 243-290
7. Altenbach C., et al. High-resolution distance mapping in rhodopsin reveals the pattern of helix movement due to activation. Proc. Natl. Acad. Sci. U. S. A. 105 (2008) 7439-7444
8. Schwartz T.W., et al. Molecular mechanism of 7TM receptor activation - a global toggle switch model. Annu. Rev. Pharmacol. Toxicol. 46 (2006) 481-519
9. Sakmar T.P., et al. Rhodopsin: insights from recent structural studies. Annu. Rev. Biophys. Biomol. Struct. 31 (2002) 443-484
10. Palczewski K., et al. Crystal structure of rhodopsin: a G protein-coupled receptor. Science 289 (2000) 739-745
11. Okada T., et al. The retinal conformation and its environment in rhodopsin in light of a new 2.2 A crystal structure. J. Mol. Biol. 342 (2004) 571-583
12. Li J., et al. Structure of bovine rhodopsin in a trigonal crystal form. J. Mol. Biol. 343 (2004) 1409-1438
13. Standfuss J., et al. Crystal structure of a thermally stable rhodopsin mutant. J. Mol. Biol. 372 (2007) 1179-1188
14. Salom D., et al. Crystal structure of a photoactivated deprotonated intermediate of rhodopsin. Proc. Natl. Acad. Sci. U. S. A. 103 (2006) 16123-16128
15. 2 adrenergic G-protein-coupled receptor. Nature 450 (2007) 383-387
16. 2-adrenergic receptor function. Science 318 (2007) 1266-1273
17. 2-adrenergic G protein-coupled receptor. Science 318 (2007) 1258-1265
18. 2-adrenergic receptor. Structure 16 (2008) 897-905
19. 1-adrenergic G-protein-coupled receptor. Nature 454 (2008) 486-491
20. 2A adenosine receptor bound to an antagonist. Science 322 (2008) 1211-1217
21. Park J.H., et al. Crystal structure of the ligand-free G-protein-coupled receptor opsin. Nature 454 (2008) 183-187
22. Scheerer P., et al. Crystal structure of opsin in its G protein-interacting conformation. Nature 455 (2008) 497-502
23. Schwartz T.W., and Hubbell W.L. Structural biology: a moving story of receptors. Nature 455 (2008) 473-474
24. Murakami M., and Kouyama T. Crystal structure of squid rhodopsin. Nature 453 (2008) 363-367
25. Shimamura T., et al. Crystal structure of squid rhodopsin with intracellularly extended cytoplasmic region. J. Biol. Chem. 283 (2008) 17753-17756
26. Storjohann L., et al. A second disulfide bridge from the N-terminal domain to extracellular loop 2 dampens receptor activity in GPR39. Biochemistry 47 (2008) 9198-9207
27. 2-adrenergic receptor. Mol. Pharmacol. 66 (2004) 356-363
28. Elling C.E., et al. Metal-ion site engineering indicating a global toggle switch model for 7TM receptor activation. J. Biol. Chem. 281 (2006) 17337-17343
29. Rosenkilde M.M., et al. Activation of the CXCR3 chemokine receptor through anchoring of a small molecule chelator ligand between TM-III, -IV, and -VI. Mol. Pharmacol. 71 (2007) 930-941
30. Kobilka B. Agonist binding: a multistep process. Mol. Pharmacol. 65 (2004) 1060-1062
31. Farrens D.L., et al. Requirement of rigid-body motion of transmembrane helices for light activation of rhodopsin. Science 274 (1996) 768-770
32. 2 adrenoceptor. EMBO J. 16 (1997) 6737-6747
33. 2-adrenoceptor. Nat. Chem. Biol. 2 (2006) 417-422
34. 2 adrenergic receptor activation. Modulation of the proline kink in transmembrane 6 by a rotamer toggle switch. J. Biol. Chem. 277 (2002) 40989-40996
35. Crocker E., et al. Location of Trp265 in metarhodopsin II: implications for the activation mechanism of the visual receptor rhodopsin. J. Mol. Biol. 357 (2006) 163-172
36. Arnis S., and Hofmann K.P. Two different forms of metarhodopsin II: Schiff base deprotonation precedes proton uptake and signaling state. Proc. Natl. Acad. Sci. U. S. A. 90 (1993) 7849-7853
37. Prioleau C., et al. Conserved helix 7 tyrosine acts as a multistate conformational switch in the 5HT2C receptor. Identification of a novel 'locked-on' phenotype and double revertant mutations. J. Biol. Chem. 277 (2002) 36577-36584
38. Fritze O., et al. Role of the conserved NPxxY(x)5,6F motif in the rhodopsin ground state and during activation. Proc. Natl. Acad. Sci. U. S. A. 100 (2003) 2290-2295
39. 2-adrenergic receptor. Biochemistry 34 (1995) 15407-15414
40. Mirzadegan T., et al. Sequence analyses of G-protein-coupled receptors: similarities to rhodopsin. Biochemistry 42 (2003) 2759-2767
41. Rovati G.E., et al. The highly conserved DRY motif of class A G protein-coupled receptors: beyond the ground state. Mol. Pharmacol. 71 (2007) 959-964
42. Ballesteros J., et al. Functional microdomains in G-protein-coupled receptors. The conserved arginine-cage motif in the gonadotropin-releasing hormone receptor. J. Biol. Chem. 273 (1998) 10445-10453
43. 1B-adrenergic receptor: role of highly conserved polar amino acids in receptor activation. EMBO J. 15 (1996) 3566-3578
44. Arnis S., et al. A conserved carboxylic acid group mediates light-dependent proton uptake and signaling by rhodopsin. J. Biol. Chem. 269 (1994) 23879-23881
45. 2-adrenergic receptor involves disruption of an ionic lock between the cytoplasmic ends of transmembrane segments 3 and 6. J. Biol. Chem. 276 (2001) 29171-29177
46. Vogel R., et al. Functional role of the 'ionic lock' - an interhelical hydrogen-bond network in family A heptahelical receptors. J. Mol. Biol. 380 (2008) 648-655
47. Knierim B., et al. Sequence of late molecular events in the activation of rhodopsin. Proc. Natl. Acad. Sci. U. S. A. 104 (2007) 20290-20295
48. Mahalingam M., et al. Two protonation switches control rhodopsin activation in membranes. Proc. Natl. Acad. Sci. U. S. A. 105 (2008) 17795-17800
49. Schwartz T.W., and Holst B. Molecular structure and function of 7TM/G-protein coupled receptors. In: Forman J.C., and Johansen T. (Eds). Textbook of Receptor Pharmacology (2002), CRC Press 65-84
50. Okada T., et al. Functional role of internal water molecules in rhodopsin revealed by X-ray crystallography. Proc. Natl. Acad. Sci. U. S. A. 99 (2002) 5982-5987
51. Pardo L., et al. The role of internal water molecules in the structure and function of the rhodopsin family of G protein-coupled receptors. ChemBioChem 8 (2007) 19-24
52. Schertler G.F. Signal transduction: the rhodopsin story continued. Nature 453 (2008) 292-293
53. 1 receptor activation. Nat. Chem. Biol. 1 (2005) 98-103
54. Urizar E., et al. An activation switch in the rhodopsin family of G protein-coupled receptors: the thyrotropin receptor. J. Biol. Chem. 280 (2005) 17135-17141
55. Monod J., et al. On the nature of allosteric transitions: a plausible model. J. Mol. Biol. 12 (1965) 88-118
56. Changeux J.P., and Edelstein S.J. Allosteric mechanisms of signal transduction. Science 308 (2005) 1424-1428
57. De Lean A., et al. A ternary complex model explains the agonist-specific binding properties of the adenylate cyclase coupled β-adrenergic receptor. J. Biol. Chem. 255 (1980) 7108-7117
58. Kenakin T. Principles: receptor theory in pharmacology. Trends Pharmacol. Sci. 25 (2004) 186-192
59. Holst B., et al. Identification of an efficacy switch region in the ghrelin receptor responsible for interchange between agonism and inverse agonism. J. Biol. Chem. 282 (2007) 15799-15811
60. Kenakin T. Functional selectivity through protean and biased agonism: who steers the ship?. Mol. Pharmacol. 72 (2007) 1393-1401
61. Neubig R.R. Missing links: mechanisms of protean agonism. Mol. Pharmacol. 71 (2007) 1200-1202
62. Weis W.I., and Kobilka B.K. Structural insights into G-protein-coupled receptor activation. Curr. Opin. Struct. Biol. 18 (2008) 734-740
63. Ahuja S., et al. Helix movement is coupled to displacement of the second extracellular loop in rhodopsin activation. Nat. Struct. Mol. Biol. 16 (2009) 168-175
64. Baldwin J.M. The probable arrangement of the helices in G protein-coupled receptors. EMBO J. 12 (1993) 1693-1703
65. Schwartz T.W. Locating ligand-binding sites in 7TM receptors by protein engineering. Curr. Opin. Biotechnol. 5 (1994) 434-444
66. Ballesteros J.A., and Weinstein H. Integrated methods for the construction of three-dimensional models and computational probing of structure-function relations in G protein-coupled receptors. In: Sealfon S.C. (Ed). Receptor Molecular Biology (1995), Academic Press 366-428