Transmembrane signal transduction by peptide hormones via family B G protein-coupled receptors

Frontiers in Pharmacology

Volumn 6, Issue NOV, 2015, Pages

  Culhane, Kelly J ^a   Liu, Yuting ^a   Cai, Yingying ^a   Yan, Elsa C Y ^a  

^a YALE UNIVERSITY   (United States)

Author keywords

Activation mechanisms; Family B GPCR; G protein; GPCR; Peptide hormone; Signal transduction

Indexed keywords

CHAPERONE; CORTICOTROPIN RELEASING FACTOR RECEPTOR 1; CYTOSKELETON PROTEIN; FAMIY B G PROTEIN COUPLED RECEPTOR; G PROTEIN COUPLED RECEPTOR; GLUCAGON RECEPTOR; GUANINE NUCLEOTIDE BINDING PROTEIN; PDZ PROTEIN; PEPTIDE HORMONE; RECEPTOR ACTIVITY MODIFYING PROTEIN; UNCLASSIFIED DRUG;

ALLOSTERISM; ALPHA HELIX; AMINO TERMINAL SEQUENCE; BINDING AFFINITY; LIGAND BINDING; MOLECULAR RECOGNITION; PROTEIN DOMAIN; PROTEIN FUNCTION; PROTEIN PROTEIN INTERACTION; RECEPTOR UPREGULATION; REVIEW; SEQUENCE ALIGNMENT; SIGNAL TRANSDUCTION; STRUCTURE ANALYSIS;

EID: 84949791792     PISSN: None     EISSN: 16639812     Source Type: Journal    
DOI: 10.3389/fphar.2015.00264     Document Type: Review

References (174)

1. Adelhorst, K., Hedegaard, B. B., Knudsen, L. B., and Kirk, O. (1994). Structure-activity studies of glucagon-like peptide-1. J. Biol. Chem. 269, 6275-6278.
2. Ahuja, S., Hornak, V., Yan, E. C. Y., Syrett, N., Goncalves, J. A., Hirshfeld, A., et al. (2009). Helix movement is coupled to displacement of the second extracellular loop in rhodopsin activation. Nat. Struct. Mol. Biol. 16, 168-175. doi: 10.1038/nsmb.1549
3. Altenbach, C., Kusnetzow, A. K., Ernst, O. P., Hofmann, K. P., and Hubbell, W. L. (2008). High-resolution distance mapping in rhodopsin reveals the pattern of helix movement due to activation. Proc. Natl. Acad. Sci. U.S.A. 105, 7439-7444. doi: 10.1073/pnas.0802515105
4. Archbold, J. K., Flanagan, J. U., Watkins, H. A., Gingell, J. J., and Hay, D. L. (2011). Structural insights into RAMP modification of secretin family G protein-coupled receptors: implications for drug development. Trends Pharmacol. Sci. 32, 591-600. doi: 10.1016/j.tips.2011.05.007
5. Ardura, J. A., and Friedman, P. A. (2011). Regulation of G Protein-Coupled Receptor Function by Na+/H+ Exchange Regulatory Factors. Pharmacol. Rev. 63, 882-900. doi: 10.1124/pr.110.004176
6. Assil-Kishawi, I., Samra, T. A., Mierke, D. F., and Abou-Samra, A. B. (2008). Residue 17 of sauvagine cross-links to the first transmembrane domain of corticotropin-releasing factor receptor 1 (CRFR1). J. Biol. Chem. 283, 35644-35651. doi: 10.1074/jbc. M806351200
7. Ayoub, M. A., and Pin, J.-P. (2013). Interaction of protease-activated receptor 2 with G proteins and β-arrestin 1 studied by bioluminescence resonance energy transfer. Front. Endocrinol. 4:196. doi: 10.3389/fendo.2013.00196
8. Ballesteros, J. A., Jensen, A. D., Liapakis, G., Rasmussen, S. G., Shi, L., Gether, U., et al. (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. doi: 10.1074/jbc. M103747200
9. Banerjee, S., Evanson, J., Harris, E., Lowe, S. L., Thomasson, K. A., and Porter, J. E. (2006). Identification of specific calcitonin-like receptor residues important for calcitonin gene-related peptide high affinity binding. BMC Pharmacol. 6:9. doi: 10.1186/1471-2210-6-9
10. Banerjee, S., Huber, T., and Sakmar, T. P. (2008). Rapid incorporation of functional rhodopsin into nanoscale apolipoprotein bound bilayer (NABB) particles. J. Mol. Biol. 377, 1067-1081. doi: 10.1016/j.jmb.2008.01.066
11. Barwell, J., Conner, A., and Poyner, D. R. (2011). Extracellular loops 1 and 3 and their associated transmembrane regions of the calcitonin receptor-like receptor are needed for CGRP receptor function. Biochim. Biophys. Acta Mol. Cell Res. 1813, 1906-1916. doi: 10.1016/j.bbamcr.2011.06.005
12. Barwell, J., Miller, P. S., Donnelly, D., and Poyner, D. R. (2010). Mapping interaction sites within the N-terminus of the calcitonin gene-related peptide receptor; the role of residues 23-60 of the calcitonin receptor-like receptor. Peptides 31, 170-176. doi: 10.1016/j.peptides.2009.10.021
13. Bavec, A., Hallbrink, M., Langel, U., and Zorko, M. (2003). Different role of intracellular loops of glucagon-like peptide-1 receptor in G-protein coupling. Regul. Pept. 111, 137-144. doi: 10.1016/S0167-0115(02)00282-3
14. Bergwitz, C., Gardella, T. J., Flannery, M. R., Potts, J. T., Kronenberg, H. M., Goldring, S. R., et al. (1996). Full activation of chimeric receptors by hybrids between parathyroid hormone and calcitonin: evidence for a common pattern of ligand-receptor interaction. J. Biol. Chem. 271, 26469-26472. doi: 10.1074/jbc.271.43.26469
15. Bortolato, A., Doré, A. S., Hollenstein, K., Tehan, B. G., Mason, J. S., and Marshall, F. H. (2014). Structure of Class B GPCRs: new horizons for drug discovery. Br. J. Pharmacol. 171, 3132-3145. doi: 10.1111/bph.12689
16. Bourgault, S., Vaudry, D., Ségalas-Milazzo, I., Guilhaudis, L., Couvineau, A., Laburthe, M., et al. (2009). Molecular and conformational determinants of pituitary adenylate cyclase-activating polypeptide (PACAP) for activation of the PAC1 receptor. J. Med. Chem. 52, 3308-3316. doi: 10.1021/jm900291j
17. Cascieri, M. A., Koch, G. E., Ber, E., Sadowski, S. J., Louizides, D., De Laszlo, S. E., et al. (1999). Characterization of a novel, non-peptidyl antagonist of the human glucagon receptor. J. Biol. Chem. 274, 8694-8697. doi: 10.1074/jbc.274.13.8694
18. Ceraudo, E., Hierso, R., Tan, Y. V., Murail, S., Rouyer-Fessard, C., Nicole, P., et al. (2012). Spatial proximity between the VPAC1 receptor and the amino terminus of agonist and antagonist peptides reveals distinct sites of interaction. FASEB J. 26, 2060-2071. doi: 10.1096/fj.11-196444
19. Ceraudo, E., Murail, S., Tan, Y.-V., Lacapère, J.-J., Neumann, J.-M., Couvineau, A., et al. (2008). The vasoactive intestinal peptide (VIP) α-Helix up to C terminus interacts with the N-terminal ectodomain of the human VIP/pituitary adenylate cyclase-activating peptide 1 receptor: photoaffinity, molecular modeling, and dynamics. Mol. Endocrinol. 22, 147-155. doi: 10.1210/me.2007-0361
20. Chen, Q., Pinon, D. I., Miller, L. J., and Dong, M. (2009). Molecular basis of glucagon-like peptide 1 docking to its intact receptor studied with carboxyl-terminal photolabile probes. J. Biol. Chem. 284, 34135-34144. doi: 10.1074/jbc. M109.038109
21. Cherezov, V., Rosenbaum, D. M., Hanson, M. A., Rasmussen, S. G., Thian, F. S., Kobilka, T. S., et al. (2007). High-resolution crystal structure of an engineered human beta2-adrenergic G protein-coupled receptor. Science 318, 1258-1265. doi: 10.1126/science.1150577
22. Chien, E. Y., Liu, W., Zhao, Q., Katritch, V., Han, G. W., Hanson, M. A., et al. (2010). Structure of the human dopamine D3 receptor in complex with a D2/D3 selective antagonist. Science 330, 1091-1095. doi: 10.1126/science.1197410
23. Choe, H.-W., Kim, Y. J., Park, J. H., Morizumi, T., Pai, E. F., Krauß, N., et al. (2011). Crystal structure of metarhodopsin II. Nature 471, 651-655. doi: 10.1038/nature09789
24. Christopoulos, A., Christopoulos, G., Morfis, M., Udawela, M., Laburthe, M., Couvineau, A., et al. (2003). Novel receptor partners and function of receptor activity-modifying proteins. J. Biol. Chem. 278, 3293-3297. doi: 10.1074/jbc. C200629200
25. Conner, A. C., Simms, J., Conner, M. T., Wootten, D. L., Wheatley, M., and Poyner, D. R. (2006). Diverse functional motifs within the three intracellular loops of the CGRP(1) receptor. Biochemistry 45, 12976-12985. doi: 10.1021/bi0615801
26. Coopman, K., Wallis, R., Robb, G., Brown, A. J., Wilkinson, G. F., Timms, D., et al. (2011). Residues within the transmembrane domain of the glucagon-like peptide-1 receptor involved in ligand binding and receptor activation: modelling the ligand-bound receptor. Mol. Endocrinol. 25, 1804-1818. doi: 10.1210/me.2011-1160
27. Couvineau, A., Gaudin, P., Maoret, J. J., Rouyerfessard, C., Nicole, P., and Laburthe, M. (1995). Highly conserved Aspartate 68, Tryptophane 73 and Glycine 109 in the N-terminal extracellular domain of the human VIP receptor are essential for its ability to bind VIP. Biochem. Biophys. Res. Commun. 206, 246-252. doi: 10.1006/bbrc.1995.1034
28. Couvineau, A., and Laburthe, M. (2012). The family B1 GPCR: structural aspects and interaction with accessory proteins. Curr. Drug Targets 13, 103-115. doi: 10.2174/138945012798868434
29. Crocker, E., Eilers, M., Ahuja, S., Hornak, V., Hirshfeld, A., Sheves, M., et al. (2006). Location of Trp265 in metarhodopsin II: implications for the activation mechanism of the visual receptor rhodopsin. J. Mol. Biol. 357, 163-172. doi: 10.1016/j.jmb.2005.12.046
30. Cypess, A. M., Unson, C. G., Wu, C. R., and Sakmar, T. P. (1999). Two cytoplasmic loops of the glucagon receptor are required to elevate cAMP or intracellular calcium. J. Biol. Chem. 274, 19455-19464. doi: 10.1074/jbc.274.27.19455
31. Dean, T., Vilardaga, J. P., Potts, J. T., and Gardella, T. J. (2008). Altered selectivity of parathyroid hormone (PTH) and PTH-Related protein (PTHrP) for distinct conformations of the PTH/PTHrP receptor. Mol. Endocrinol. 22, 156-166. doi: 10.1210/me.2007-0274
32. Denton, E. V., Craig, C. J., Pongratz, R. L., Appelbaum, J. S., Doerner, A. E., Narayanan, A., et al. (2013). A β-peptide agonist of the GLP-1 receptor, a class B GPCR. Org. Lett. 15, 5318-5321. doi: 10.1021/ol402568j
33. Deupi, X., Edwards, P., Singhal, A., Nickle, B., Oprian, D., Schertler, G., et al. (2012). Stabilized G protein binding site in the structure of constitutively active metarhodopsin-II. Proc. Natl. Acad. Sci. U.S.A. 109, 119-124. doi: 10.1073/pnas.1114089108
34. Di Paolo, E., De Neef, P., Moguilevsky, N., Petry, H., Bollen, A., Waelbroeck, M., et al. (1998). Contribution of the second transmembrane helix of the secretin receptor to the positioning of secretin. FEBS Lett. 424, 207-210. doi: 10.1016/S0014-5793(98)00175-6
35. Di Paolo, E., Petry, H., Moguilevsky, N., Bollen, A., De Neef, P., Waelbroeck, M., et al. (1999). Mutations of aromatic residues in the first transmembrane helix impair signalling by the secretin receptor. Recept. Channels 6, 309-315.
36. Dong, M., Lam, P. C.-H., Pinon, D. I., Hosohata, K., Orry, A., Sexton, P. M., et al. (2011a). Molecular basis of secretin docking to its intact receptor using multiple photolabile probes distributed throughout the pharmacophore. J. Biol. Chem. 286, 23888-23899. doi: 10.1074/jbc. M111.245969
37. Dong, M., Lam, P. C.-H., Pinon, D. I., Sexton, P. M., Abagyan, R., and Miller, L. J. (2008). Spatial approximation between secretin residue five and the third extracellular loop of its receptor provides new insight into the molecular basis of natural agonist binding. Mol. Pharmacol. 74, 413-422. doi: 10.1124/mol.108.047209
38. Dong, M., Le, A., Te, J. A., Pinon, D. I., Bordner, A. J., and Miller, L. J. (2011b). Importance of each residue within secretin for receptor binding and biological activity. Biochemistry 50, 2983-2993. doi: 10.1021/bi200133u
39. Dong, M., Pinon, D. I., Cox, R. F., and Miller, L. J. (2004). Importance of the amino terminus in secretin family g protein-coupled receptors: intrinsic photoaffinity labeling establishes initial docking constraints for the calcitonin receptor. J. Biol. Chem. 279, 1167-1175. doi: 10.1074/jbc. M305719200
40. Dong, M., Pinon, D. I., and Miller, L. J. (2013). Insights into the impact of phenolic residue incorporation at each position along secretin for receptor binding and biological activity. Regul. Pept. 180, 5-11. doi: 10.1016/j.regpep.2012.10.001
41. Dong, M., Xu, X., Ball, A. M., Makhoul, J. A., Lam, P. C.-H., Pinon, D. I., et al. (2012). Mapping spatial approximations between the amino terminus of secretin and each of the extracellular loops of its receptor using cysteine trapping. FASEB J. 26, 5092-5105. doi: 10.1096/fj.12-212399
42. Dong, M., Zang, M., Pinon, D. I., Li, Z., Lybrand, T. P., and Miller, L. J. (2002). Interaction among four residues distributed through the secretin pharmacophore and a focused region of the secretin receptor amino terminus. Mol. Endocrinol. 16, 2490-2501. doi: 10.1210/me.2002-0111
43. Donnelly, D. (2012). The structure and function of the glucagon-like peptide-1 receptor and its ligands. Br. J. Pharmacol. 166, 27-41. doi: 10.1111/j.1476-5381.2011.01687.x
44. Du, K., Nicole, P., Couvineau, A., and Laburthe, M. (1997). Aspartate 196 in the first extracellular loop of the human VIP1 receptor is essential for VIP binding and VIP-stimulated cAMP production. Biochem. Biophys. Res. Commun. 230, 289-292. doi: 10.1006/bbrc.1996.5949
45. Dunham, T. D., and Farrens, D. L. (1999). Conformational changes in rhodopsin-movement of helix F detected by site-specific chemical labeling and fluorescence spectroscopy. J. Biol. Chem. 274, 1683-1690. doi: 10.1074/jbc.274.3.1683
46. El Moustaine, D., Granier, S., Doumazane, E., Scholler, P., Rahmeh, R., Bron, P., et al. (2012). Distinct roles of metabotropic glutamate receptor dimerization in agonist activation and G-protein coupling. Proc. Natl. Acad. Sci. U.S.A. 109, 16342-16347. doi: 10.1073/pnas.1205838109
47. Fahmy, K., Sakmar, T. P., and Siebert, F. (2000). Transducin-dependent protonation of glutamic acid 134 in Rhodopsin. Biochemistry 39, 10607-10612. doi: 10.1021/bi000912d
48. Ferrandon, S., Feinstein, T. N., Castro, M., Wang, B., Bouley, R., Potts, J. T., et al. (2009). Sustained cyclic AMP production by parathyroid hormone receptor endocytosis. Nat. Chem. Biol. 5, 734-742. doi: 10.1038/nchembio.206
49. Fredriksson, R., Lagerstrom, M. C., Lundin, L. G., and Schioth, H. B. (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. doi: 10.1124/mol.63.6.1256
50. Fritze, O., Filipek, S., Kuksa, V., Palczewski, K., Hofmann, K. P., and Ernst, O. P. (2003). 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, 2290-2295. doi: 10.1073/pnas.0435715100
51. Galés, C., Rebois, R. V., Hogue, M., Trieu, P., Breit, A., Hébert, T. E., et al. (2005). Real-time monitoring of receptor and G-protein interactions in living cells. Nat. Methods 2, 177-184. doi: 10.1038/nmeth743
52. Galés, C., Van Durm, J. J. J., Schaak, S., Pontier, S., Percherancier, Y., Audet, M., et al. (2006). Probing the activation-promoted structural rearrangements in preassembled receptor-G protein complexes. Nat. Struct. Mol. Biol. 13, 778-786. doi: 10.1038/nsmb1134
53. Gao, F., Harikumar, K. G., Dong, M., Lam, P. C.-H., Sexton, P. M., Christopoulos, A., et al. (2009). Functional importance of a structurally distinct homodimeric complex of the family BG protein-coupled secretin receptor. Mol. Pharmacol. 76, 264-274. doi: 10.1124/mol.109.055756
54. Garcia, G. L., Dong, M. Q., and Miller, L. J. (2012). Differential determinants for coupling of distinct G proteins with the class B secretin receptor. Am. J. Physiol. Cell Physiol. 302, C1202-C1212. doi: 10.1152/ajpcell.00273.2011
55. Gardella, T. J., and Jüppner, H. (2001). Molecular properties of the PTH/PTHrP receptor. Trends Endocrinol. Metab. 12, 210-217. doi: 10.1016/S1043-2760(01)00409-X
56. Gensure, R. C., Shimizu, N., Tsang, J., and Gardella, T. J. (2003). Identification of a contact site for residue 19 of parathyroid hormone (PTH) and PTH-related protein analogs in transmembrane domain two of the type 1 PTH receptor. Mol. Endocrinol. 17, 2647-2658. doi: 10.1210/me.2003-0275
57. Gilman, A. G. (1987). G-proteins-transducers of receptor-generated signals. Annu. Rev. Biochem. 56, 615-649. doi: 10.1146/annurev.bi.56.070187.003151
58. Gkountelias, K., Tselios, T., Venihaki, M., Deraos, G., Lazaridis, I., Rassouli, O., et al. (2009). Alanine scanning mutagenesis of the second extracellular loop of type 1 corticotropin-releasing factor receptor revealed residues critical for peptide binding. Mol. Pharmacol. 75, 793-800. doi: 10.1124/mol.108.052423
59. Grace, C. R. R., Perrin, M. H., Digruccio, M. R., Miller, C. L., Rivier, J. E., Vale, W. W., et al. (2004). NMR structure and peptide hormone binding site of the first extracellular domain of a type B1 G protein-coupled receptor. Proc. Natl. Acad. Sci. U.S.A. 101, 12836-12841. doi: 10.1073/pnas.0404702101
60. Grace, C. R. R., Perrin, M. H., Gulyas, J., Digruccio, M. R., Cantle, J. P., Rivier, J. E., et al. (2007). Structure of the N-terminal domain of a type B1 G protein-coupled receptor in complex with a peptide ligand. Proc. Natl. Acad. Sci. U.S.A. 104, 4858-4863. doi: 10.1073/pnas.0700682104
61. Gurevich, V. V., and Gurevich, E. V. (2008). GPCR monomers and oligomers: it takes all kinds. Trends Neurosci. 31, 74-81. doi: 10.1016/j.tins.2007.11.007
62. Hallbrink, M., Holmqvist, T., Olsson, M., Ostenson, C. G., Efendic, S., and Langel, U. (2001). Different domains in the third intracellular loop of the GLP-1 receptor are responsible for Galpha(s) and Galpha(i)/Galpha(o) activation. Biochim. Biophys. Acta 1546, 79-86. doi: 10.1016/S0167-4838(00)00270-3
63. Harikumar, K. G., Wootten, D., Pinon, D. I., Koole, C., Ball, A. M., Furness, S. G., et al. (2012). Glucagon-like peptide-1 receptor dimerization differentially regulates agonist signaling but does not affect small molecule allostery. Proc. Natl. Acad. Sci. U.S.A. 109, 18607-18612. doi: 10.1073/pnas.1205227109
64. Heller, R. S., Kieffer, T. J., and Habener, J. F. (1996). Point mutations in the first and third intracellular loops of the glucagon-like peptide-1 receptor alter intracellular signaling. Biochem. Biophys. Res. Commun. 223, 624-632. doi: 10.1006/bbrc.1996.0945
65. Hjorth, S. A., Orskov, C., and Schwartz, T. W. (1998). Constitutive activity of glucagon receptor mutants. Mol. Endocrinol. 12, 78-86. doi: 10.1210/mend.12.1.0045
66. Hoare, S. R. (2005). Mechanisms of peptide and nonpeptide ligand binding to Class B G-protein-coupled receptors. Drug Discov. Today 10, 417-427. doi: 10.1016/S1359-6446(05)03370-2
67. Hoare, S. R., Brown, B. T., Santos, M. A., Malany, S., Betz, S. F., and Grigoriadis, D. E. (2006). Single amino acid residue determinants of non-peptide antagonist binding to the corticotropin-releasing factor1 (CRF1) receptor. Biochem. Pharmacol. 72, 244-255. doi: 10.1016/j.bcp.2006.04.007
68. Hoare, S. R. J., Gardella, T. J., and Usdin, T. B. (2001). Evaluating the signal transduction mechanism of the parathyroid hormone 1 receptor-effect of receptor-G-protein interaction on the ligand binding mechanism and receptor conformation. J. Biol. Chem. 276, 7741-7753. doi: 10.1074/jbc. M009395200
69. Hollenstein, K., De Graaf, C., Bortolato, A., Wang, M.-W., Marshall, F. H., and Stevens, R. C. (2014). Insights into the structure of class B GPCRs. Trends Pharmacol. Sci. 35, 12-22. doi: 10.1016/j.tips.2013.11.001
70. Hollenstein, K., Kean, J., Bortolato, A., Cheng, R. K., Doré, A. S., Jazayeri, A., et al. (2013). Structure of class B GPCR corticotropin-releasing factor receptor 1. Nature 449, 438-443. doi: 10.1038/nature12357
71. Huang, Z. M., Chen, Y., Pratt, S., Chen, T. H., Bambino, T., Nissenson, R. A., et al. (1996). The N-terminal region of the third intracellular loop of the parathyroid hormone (PTH)/PTH-related peptide receptor is critical for coupling to cAMP and inositol phosphate/Ca2+ signal transduction pathways. J. Biol. Chem. 271, 33382-33389. doi: 10.1074/jbc.271.52.33382
72. Igarashi, H., Ito, T., Hou, W., Mantey, S. A., Pradhan, T. K., Ulrich, C. D., et al. (2002a). Elucidation of vasoactive intestinal peptide pharmacophore for VPAC1 receptors in human, rat, and guinea pig. J. Pharmacol. Exp. Ther. 301, 37-50. doi: 10.1124/jpet.301.1.37
73. Igarashi, H., Ito, T., Pradhan, T. K., Mantey, S. A., Hou, W., Coy, D. H., et al. (2002b). Elucidation of the vasoactive intestinal peptide pharmacophore for VPAC2 receptors in human and rat and comparison to the pharmacophore for VPAC1 receptors. J. Pharmacol. Exp. Ther. 303, 445-460. doi: 10.1371/journal.pone.0019682
74. Iidaklein, A., Guo, J., Takemura, M., Drakes, M. T., Potts, J. T., Abousamra, A., et al. (1997). Mutations in the second cytoplasmic loop of the rat parathyroid hormone (PTH)/PTH-related protein receptor result in selective loss of PTH-stimulated phospholipase C activity. J. Biol. Chem. 272, 6882-6889. doi: 10.1074/jbc.272.11.6882
75. Inagaki, S., Ghirlando, R., White, J. F., Gvozdenovic-Jeremic, J., Northup, J. K., and Grisshammer, R. (2012). Modulation of the interaction between neurotensin receptor NTS1 and Gq protein by lipid. J. Mol. Biol. 417, 95-111. doi: 10.1016/j.jmb.2012.01.023
76. Jaakola, V. P., Griffith, M. T., Hanson, M. A., Cherezov, V., Chien, E. Y. T., Lane, J. R., et al. (2008). The 2.6 angstrom crystal structure of a human A(2A) adenosine receptor bound to an antagonist. Science 322, 1211-1217. doi: 10.1126/science.1164772
77. Janz, J. M., and Farrens, D. L. (2004). Rhodopsin activation exposes a key hydrophobic binding site for the transducin α-subunit C terminus. J. Biol. Chem. 279, 29767-29773. doi: 10.1074/jbc. M402567200
78. Jastrzebska, B., Tsybovsky, Y., and Palczewski, K. (2010). Complexes between photoactivated rhodopsin and transducin: progress and questions. Biochem. J. 428, 1-10. doi: 10.1042/BJ20100270
79. Johnson, L. M., Barrick, S., Hager, M. V., McFedries, A., Homan, E. A., Rabaglia, M. E., et al. (2014). A potent a/β-peptide analogue of GLP-1 with prolonged action in vivo. J. Am. Chem. Soc. 136, 12848-12851. doi: 10.1021/ja507168t
80. Kirkpatrick, A., Heo, J., Abrol, R., and Goddard, W. A. (2012). Predicted structure of agonist-bound glucagon-like peptide 1 receptor, a class BG protein-coupled receptor. Proc. Natl. Acad. Sci. U.S.A. 109, 19988-19993. doi: 10.1073/pnas.1218051109
81. Kobilka, B. K., and Deupi, X. (2007). Conformational complexity of G-protein-coupled receptors. Trends Pharmacol. Sci. 28, 397-406. doi: 10.1016/j.tips.2007.06.003
82. Koole, C., Wootten, D., Simms, J., Miller, L. J., Christopoulos, A., and Sexton, P. M. (2012). Second extracellular loop of human glucagon-like peptide-1 receptor (GLP-1R) has a critical role in GLP-1 peptide binding and receptor activation. J. Biol. Chem. 287, 3642-3658. doi: 10.1074/jbc. M111.309328
83. Koth, C. M., Murray, J. M., Mukund, S., Madjidi, A., Minn, A., Clarke, H. J., et al. (2012). Molecular basis for negative regulation of the glucagon receptor. Proc. Natl. Acad. Sci. U.S.A. 109, 14393-14398. doi: 10.1073/pnas.1206734109
84. Kumar, S., Pioszak, A., Zhang, C. H., Swaminathan, K., and Xu, H. E. (2011). Crystal structure of the PAC1R extracellular domain unifies a consensus fold for hormone recognition by Class B G-protein coupled receptors. PLoS ONE 6:e19682. doi: 10.1371/journal.pone.0019682
85. Kusano, S., Kukimoto-Niino, M., Hino, N., Ohsawa, N., Okuda, K., Sakamoto, K., et al. (2012). Structural basis for extracellular interactions between calcitonin receptor-like receptor and receptor activity-modifying protein 2 for adrenomedullin-specific binding. Protein Sci. 21, 199-210. doi: 10.1002/pro.2003
86. Lagerstrom, M. C., and Schioth, H. B. (2008). Structural diversity of G protein-coupled receptors and significance for drug discovery. Nat. Rev. Drug Discov. 7, 339-357. doi: 10.1038/nrd2518
87. Langer, I., Vertongen, P., Perret, J., Waelbroeck, M., and Robberecht, P. (2002). A small sequence in the third intracellular loop of the VPAC(1) receptor is responsible for its efficient coupling to the calcium effector. Mol. Endocrinol. 16, 1089-1096. doi: 10.1210/mend.16.5.0822
88. Leitz, A. J., Bayburt, T. H., Barnakov, A. N., Springer, B. A., and Sligar, S. G. (2006). Functional reconstitution of beta(2)-adrenergic receptors utilizing self-assembling Nanodisc technology. Biotechniques 40, 601-602. doi: 10.2144/000112169
89. Liaw, C. W., Grigoriadis, D. E., Lovenberg, T. W., De Souza, E. B., and Maki, R. A. (1997). Localization of ligand-binding domains of human corticotropin-releasing factor receptor: a chimeric receptor approach. Mol. Endocrinol. 11, 980-985. doi: 10.1210/mend.11.7.9946
90. Liu, Y., Cai, Y., Liu, W., Li, X.-H., Rhoades, E., and Yan, E. C. Y. (2015). Triblock peptide-linker-lipid molecular design improves potency of peptide ligands targeting family B G protein-coupled receptors. Chem. Commun. 51, 6157-6160. doi: 10.1039/C5CC00301F
91. Ma, Z., Du, L., and Li, M. (2014). Toward fluorescent probes for G-Protein-Coupled Receptors (GPCRs). J. Med. Chem. 57, 8187-8203. doi: 10.1021/jm401823z
92. Mahalingam, M., Martinez-Mayorga, K., Brown, M. F., and Vogel, R. (2008). Two protonation switches control rhodopsin activation in membranes. Proc. Natl. Acad. Sci. U.S.A. 105, 17795-17800. doi: 10.1073/pnas.0804541105
93. Mahon, M. J., Donowitz, M., Yun, C. C., and Segre, G. V. (2002). Na(+)/H(+) exchanger regulatory factor 2 directs parathyroid hormone 1 receptor signalling. Nature 417, 858-861. doi: 10.1038/nature00816
94. Mahon, M. J., and Segre, G. V. (2004). Stimulation by parathyroid hormone of a NHERF-1-assembled complex consisting of the parathyroid hormone I receptor, phospholipase C beta, and actin increases intracellular calcium in opossum kidney cells. J. Biol. Chem. 279, 23550-23558. doi: 10.1074/jbc. M313229200
95. Mahon, M. J., and Shimada, M. (2005). Calmodulin interacts with the cytoplasmic tails of the parathyroid hormone 1 receptor and a sub-set of class b G-protein coupled receptors. FEBS Lett. 579, 803-807. doi: 10.1016/j.febslet.2004.12.056
96. Mannstadt, M., Jüppner, H., and Gardella, T. J. (1999). Receptors for PTH and PTHrP: their biological importance and functional properties. Am. J. Physiol. Renal Physiol. 277, F665-F675.
97. Mathi, S. K., Chan, Y., Li, X. F., and Wheeler, M. B. (1997). Scanning of the glucagon-like peptide-1 receptor localizes G protein-activating determinants primarily to the N terminus of the third intracellular loop. Mol. Endocrinol. 11, 424-432. doi: 10.1210/mend.11.4.9913
98. McLatchie, L. M., Fraser, N. J., Main, M. J., Wise, A., Brown, J., Thompson, N., et al. (1998). RAMPs regulate the transport and ligand specificity of the calcitonin-receptor-like receptor. Nature 393, 333-339. doi: 10.1038/30666
99. Miller, L. J., Chen, Q., Lam, P. C.-H., Pinon, D. I., Sexton, P. M., Abagyan, R., et al. (2011). Refinement of glucagon-like peptide 1 docking to its intact receptor using mid-region photolabile probes and molecular modeling. J. Biol. Chem. 286, 15895-15907. doi: 10.1074/jbc. M110.217901
100. Mitra, N., Liu, Y. T., Liu, J., Serebryany, E., Mooney, V., Devree, B. T., et al. (2013). Calcium-dependent ligand binding and G-protein signaling of family B GPCR parathyroid hormone 1 receptor purified in nanodiscs. ACS Chem. Biol. 8, 617-625. doi: 10.1021/cb300466n
101. Moreira, I. S. (2014). Structural features of the G-protein/GPCR interactions. Biochim. Biophys. Acta 1840, 16-33. doi: 10.1016/j.bbagen.2013.08.027
102. Mukund, S., Shang, Y. L., Clarke, H. J., Madjidi, A., Corn, J. E., Kates, L., et al. (2013). Inhibitory mechanism of an allosteric antibody targeting the glucagon receptor. J. Biol. Chem. 288, 36168-36178. doi: 10.1074/jbc. M113.496984
103. Neumann, J.-M., Couvineau, A., Murail, S., Lacapère, J.-J., Jamin, N., and Laburthe, M. (2008). Class-B GPCR activation: is ligand helix-capping the key? Trends Biochem. Sci. 33, 314-319. doi: 10.1016/j.tibs.2008.05.001
104. Nicole, P., Lins, L., Rouyer-Fessard, C., Drouot, C., Fulcrand, P., Thomas, A., et al. (2000). Identification of key residues for interaction of vasoactive intestinal peptide with human VPAC1 and VPAC2 receptors and development of a highly selective VPAC1 receptor agonist: alanine scanning and molecular modeling of the peptide. J. Biol. Chem. 275, 24003-24012. doi: 10.1074/jbc. M002325200
105. Ohtaki, T., Ogi, K., Masuda, Y., Mitsuoka, K., Fujiyoshi, Y., Kitada, C., et al. (1998). Expression, purification, and reconstitution of receptor for pituitary adenylate cyclase-activating polypeptide large-scale purification of a functionally active G protein-coupled receptor produced in SF9 insect cells. J. Biol. Chem. 273, 15464-15473. doi: 10.1074/jbc.273.25.15464
106. Okada, T., Sugihara, M., Bondar, A. N., Elstner, M., Entel, P., and Buss, V. (2004). The retinal conformation and its environment in rhodopsin in light of a new 2.2 A crystal structure. J. Mol. Biol. 342, 571-583. doi: 10.1016/j.jmb.2004.07.044
107. Okazaki, M., Ferrandon, S., Vilardaga, J. P., Bouxsein, M. L., Potts, J. T., and Gardella, T. J. (2008). Prolonged signaling at the parathyroid hormone receptor by peptide ligands targeted to a specific receptor conformation (vol 105, pg 16525, 2008). Proc. Natl. Acad. Sci. U.S.A. 105, 20559-20559. doi: 10.1073/pnas.0808750105
108. Pal, K., Melcher, K., and Xu, H. E. (2012). Structure and mechanism for recognition of peptide hormones by Class B G protein coupled receptors. Acta Pharmacol. Sin. 33, 300-311. doi: 10.1038/aps.2011.170
109. Pal, K., Swaminathan, K., Xu, H. E., and Pioszak, A. A. (2010). Structural basis for hormone recognition by the human CRFR2 alpha G Protein-coupled Receptor. J. Biol. Chem. 285, 40351-40361. doi: 10.1074/jbc. M110.186072
110. Palczewski, K., Kumasaka, T., Hori, T., Behnke, C. A., Motoshima, H., Fox, B. A., et al. (2000). Crystal structure of rhodopsin: AG protein-coupled receptor. Science 289, 739-745. doi: 10.1126/science.289.5480.739
111. Pan, D., Ganim, Z., Kim, J. E., Verhoeven, M. A., Lugtenburg, J., and Mathies, R. A. (2002). Time-resolved resonance Raman analysis of chromophore structural changes in the formation and decay of rhodopsin's BSI intermediate. J. Am. Chem. Soc. 124, 4857-4864. doi: 10.1021/ja012666e
112. Parameswaran, N., and Spielman, W. S. (2006). RAMPs: the past, present and future. Trends Biochem. Sci. 31, 631-638. doi: 10.1016/j.tibs.2006.09.006
113. Parthier, C., Kleinschmidt, M., Neumann, P., Rudolph, R., Manhart, S., Schlenzig, D., et al. (2007). Crystal structure of the incretin-bound extracellular domain of a G protein-coupled receptor. Proc. Natl. Acad. Sci. U.S.A. 104, 13942-13947. doi: 10.1073/pnas.0706404104
114. Parthier, C., Reedtz-Runge, S., Rudolph, R., and Stubbs, M. T. (2009). Passing the baton in class B GPCRs: peptide hormone activation via helix induction? Trends Biochem. Sci. 34, 303-310. doi: 10.1016/j.tibs.2009.02.004
115. Perret, J., Craenenbroeck, M., Langer, I., Vertongen, P., Gregoire, F., Robberecht, P., et al. (2002). Mutational analysis of the glucagon receptor: similarities with the vasoactive intestinal peptide (VIP)/pituitary adenylate cyclase-activating peptide (PACAP)/secretin receptors for recognition of the ligand's third residue. Biochem. J. 362, 389-394. doi: 10.1042/bj3620389
116. Pham, V., Dong, M., Wade, J. D., Miller, L. J., Morton, C. J., Ng, H.-L., et al. (2005). Insights into interactions between the a-Helical region of the salmon calcitonin antagonists and the human calcitonin receptor using photoaffinity labeling. J. Biol. Chem. 280, 28610-28622. doi: 10.1074/jbc. M503272200
117. Pham, V., Wade, J. D., Purdue, B. W., and Sexton, P. M. (2004). Spatial proximity between a photolabile residue in position 19 of salmon calcitonin and the amino terminus of the human calcitonin receptor. J. Biol. Chem. 279, 6720-6729. doi: 10.1074/jbc. M307214200
118. Pioszak, A. A., Harikumar, K. G., Parker, N. R., Miller, L. J., and Xu, H. E. (2010). Dimeric arrangement of the parathyroid hormone receptor and a structural mechanism for ligand-induced dissociation. J. Biol. Chem. 285, 12435-12444. doi: 10.1074/jbc. M109.093138
119. Pioszak, A. A., Parker, N. R., Gardella, T. J., and Xu, H. E. (2009). Structural basis for parathyroid hormone-related protein binding to the parathyroid hormone receptor and design of conformation-selective peptides. J. Biol. Chem. 284, 28382-28391. doi: 10.1074/jbc. M109.022905
120. Pioszak, A. A., Parker, N. R., Suino-Powell, K., and Xu, H. E. (2008). Molecular recognition of corticotropin-releasing factor by its G-protein-coupled Receptor CRFR1. J. Biol. Chem. 283, 32900-32912. doi: 10.1074/jbc. M805749200
121. Pioszak, A. A., and Xu, H. E. (2008). Molecular recognition of parathyroid hormone by its G protein-coupled receptor. Proc. Natl. Acad. Sci. U.S.A. 105, 5034-5039. doi: 10.1073/pnas.0801027105
122. Prévost, M., Vertongen, P., Raussens, V., Roberts, D. J., Cnudde, J., Perret, J., et al. (2010). Mutational and cysteine scanning analysis of the glucagon receptor N-terminal domain. J. Biol. Chem. 285, 30951-30958. doi: 10.1074/jbc. M110.102814
123. Prioleau, C., Visiers, I., Ebersole, B. J., Weinstein, H., and Sealfon, S. C. (2002). 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, 36577-36584. doi: 10.1074/jbc. M206223200
124. Qi, T., and Hay, D. L. (2010). Structure-function relationships of the N-terminus of receptor activity-modifying proteins. Br. J. Pharmacol. 159, 1059-1068. doi: 10.1111/j.1476-5381.2009.00541.x
125. Qin, K., Dong, C., Wu, G., and Lambert, N. A. (2011). Inactive-state preassembly of Gq-coupled receptors and Gq heterotrimers. Nat. Chem. Biol. 7, 740-747. doi: 10.1038/nchembio.642
126. Rashid, A. J., O'dowd, B. F., and George, S. R. (2004). Minireview: diversity and complexity of signaling through peptidergic G protein-coupled receptors. Endocrinology 145, 2645-2652. doi: 10.1210/en.2004-0052
127. Rasmussen, S. G. F., Devree, B. T., Zou, Y., Kruse, A. C., Chung, K. Y., Kobilka, T. S., et al. (2011). Crystal structure of the [bgr]2 adrenergic receptor-Gs protein complex. Nature 477, 549-555. doi: 10.1038/nature10361
128. Ravn, P., Madhurantakam, C., Kunze, S., Matthews, E., Priest, C., O'brien, S., et al. (2013). Structural and pharmacological characterization of novel potent and selective monoclonal antibody antagonists of glucose-dependent insulinotropic polypeptide receptor. J. Biol. Chem. 288, 19760-19772. doi: 10.1074/jbc. M112.426288
129. Ritter, S. L., and Hall, R. A. (2009). Fine-tuning of GPCR activity by receptor-interacting proteins. Nat. Rev. Mol. Cell Biol. 10, 819-830. doi: 10.1038/nrm2803
130. Roberts, D. J., Vertongen, P., and Waelbroeck, M. (2011). Analysis of the glucagon receptor first extracellular loop by the substituted cysteine accessibility method. Peptides 32, 1593-1599. doi: 10.1016/j.peptides.2011.06.009
131. Roed, S. N., Orgaard, A., Jorgensen, R., and De Meyts, P. (2012). Receptor oligomerization in family B1 of G-protein-coupled receptors: focus on BRET investigations and the link between GPCR oligomerization and binding cooperativity. Front. Endocrinol. 3:62. doi: 10.3389/fendo.2012.00062
132. Runge, S., Gram, C., Brauner-Osborne, H., Madsen, K., Knudsen, L. B., and Wulff, B. S. (2003). Three distinct epitopes on the extracellular face of the glucagon receptor determine specificity for the glucagon amino terminus. J. Biol. Chem. 278, 28005-28010. doi: 10.1074/jbc. M301085200
133. Runge, S., Thogersen, H., Madsen, K., Lau, J., and Rudolph, R. (2008). Crystal structure of the ligand-bound glucagon-like peptide-1 receptor extracellular domain. J. Biol. Chem. 283, 11340-11347. doi: 10.1074/jbc. M708740200
134. Scheerer, P., Park, J. H., Hildebrand, P. W., Kim, Y. J., Krauss, N., Choe, H.-W., et al. (2008). Crystal structure of opsin in its G-protein-interacting conformation. Nature 455, 497-502. doi: 10.1038/nature07330
135. Schipani, E., Jensen, G. S., Pincus, J., Nissenson, R. A., Gardella, T. J., and Jüppner, H. (1997). Constitutive activation of the cyclic adenosine 3', 5'-monophosphate signaling pathway by parathyroid hormone (PTH)/PTH-related peptide receptors mutated at the two loci for Jansen's metaphyseal chondrodysplasia. Mol. Endocrinol. 11, 851-858.
136. Schipani, E., Kruse, K., and Jüppner, H. (1995). A constitutively active mutant PTH-PTHrP receptor in Jansen-type metaphyseal chondrodysplasia. Science 268, 98-100. doi: 10.1126/science.7701349
137. Serebryany, E., Zhu, G. A., and Yan, E. C. Y. (2012). Artificial membrane-like environments for in vitro studies of purified G-protein coupled receptors. Biochim. Biophys. Acta 1818, 225-233. doi: 10.1016/j.bbamem.2011.07.047
138. Shapiro, D. A., Kristiansen, K., Weiner, D. M., Kroeze, W. K., and Roth, B. L. (2002). Evidence for a model of agonist-induced activation of 5-hydroxytryptamine 2A serotonin receptors that involves the disruption of a strong ionic interaction between helices 3 and 6. J. Biol. Chem. 277, 11441-11449. doi: 10.1074/jbc. M111675200
139. Shimada, M., Chen, X., Cvrk, T., Hilfiker, H., Parfenova, M., and Segre, G. V. (2002). Purification and characterization of a receptor for human parathyroid hormone and parathyroid hormone-related peptide. J. Biol. Chem. 277, 31774-31780. doi: 10.1074/jbc. M204166200
140. Shimamura, T., Shiroishi, M., Weyand, S., Tsujimoto, H., Winter, G., Katritch, V., et al. (2011). Structure of the human histamine H1 receptor complex with doxepin. Nature 475, 65-70. doi: 10.1038/nature10236
141. Singh, R., Ahalawat, N., and Murarka, R. K. (2015). Activation of corticotropin-releasing factor 1 receptor: insights from molecular dynamics simulations. J. Phys. Chem. B 119, 2806-2817. doi: 10.1021/jp509814n
142. Singhal, A., Ostermaier, M. K., Vishnivetskiy, S. A., Panneels, V., Homan, K. T., Tesmer, J. J., et al. (2013). Insights into congenital stationary night blindness based on the structure of G90D rhodopsin. EMBO Rep. 14, 520-526. doi: 10.1038/embor.2013.44
143. Siu, F. Y., He, M., De Graaf, C., Han, G. W., Yang, D., Zhang, Z., et al. (2013). Structure of the human glucagon class B G-protein-coupled receptor. Nature 449, 444-449. doi: 10.1038/nature12393
144. Smith, S. O. (2010). Structure and activation of the visual pigment rhodopsin. Annu. Rev. Biophys. 39, 309-328. doi: 10.1146/annurev-biophys-101209-104901
145. Solano, R. M., Langer, I., Perret, J., Vertongen, P., Juarranz, M. G., Robberecht, P., et al. (2001). Two basic residues of the h-VPAC1 receptor second transmembrane helix are essential for ligand binding and signal transduction. J. Biol. Chem. 276, 1084-1088. doi: 10.1074/jbc. M007686200
146. Standfuss, J., Edwards, P. C., D'antona, A., Fransen, M., Xie, G., Oprian, D. D., et al. (2011). The structural basis of agonist-induced activation in constitutively active rhodopsin. Nature 471, 656-660. doi: 10.1038/nature09795
147. Stevens, R. C., Cherezov, V., Katritch, V., Abagyan, R., Kuhn, P., Rosen, H., et al. (2013). The GPCR Network: a large-scale collaboration to determine human GPCR structure and function. Nat. Rev. Drug Discov. 12, 25-34. doi: 10.1038/nrd3859
148. Sun, C., Song, D., Davis-Taber, R. A., Barrett, L. W., Scott, V. E., Richardson, P. L., et al. (2007). Solution structure and mutational analysis of pituitary adenylate cyclase-activating polypeptide binding to the extracellular domain of PAC1-RS. Proc. Natl. Acad. Sci. U.S.A. 104, 7875-7880. doi: 10.1073/pnas.0611397104
149. Takhar, S., Gyomorey, S., Su, R. C., Mathi, S. K., Li, X. F., and Wheeler, M. B. (1996). The third cytoplasmic domain of the GLP-1[7-36 amide] receptor is required for coupling to the adenylyl cyclase system. Endocrinology 137, 2175-2178.
150. Tan, Y.-V., Couvineau, A., Murail, S., Ceraudo, E., Neumann, J.-M., Lacapère, J.-J., et al. (2006). Peptide agonist docking in the N-terminal ectodomain of a Class II G protein-coupled receptor, the VPAC1 receptor photoaffinity, NMR, and molecular modeling. J. Biol. Chem. 281, 12792-12798. doi: 10.1074/jbc. M513305200
151. Tan, Y.-V., Couvineau, A., Van Rampelbergh, J., and Laburthe, M. (2003). Photoaffinity labeling demonstrates physical contact between vasoactive intestinal peptide and the N-terminal ectodomain of the human VPAC1 receptor. J. Biol. Chem. 278, 36531-36536. doi: 10.1074/jbc. M304770200
152. Tautermann, C. S. (2014). GPCR structures in drug design, emerging opportunities with new structures. Bioorg. Med. Chem. Lett. 24, 4073-4079. doi: 10.1016/j.bmcl.2014.07.009
153. Tehan, B. G., Bortolato, A., Blaney, F. E., Weir, M. P., and Mason, J. S. (2014). Unifying family A GPCR theories of activation. Pharmacol. Ther. 143, 51-60. doi: 10.1016/j.pharmthera.2014.02.004
154. ter Haar, E., Koth, C. M., Abdul-Manan, N., Swenson, L., Coll, J. T., Lippke, J. A., et al. (2010). Crystal structure of the ectodomain complex of the CGRP receptor, a Class-B GPCR, reveals the site of drug antagonism. Structure 18, 1083-1093. doi: 10.1016/j.str.2010.05.014
155. Thomas, B. E., Woznica, I., Mierke, D. F., Wittelsberger, A., and Rosenblatt, M. (2008). Conformational changes in the parathyroid hormone receptor associated with activation by agonist. Mol. Endocrinol. 22, 1154-1162. doi: 10.1210/me.2007-0520
156. Tseng, C. C., and Lin, L. (1997). A point mutation in the glucose-dependent insulinotropic peptide receptor confers constitutive activity. Biochem. Biophys. Res. Commun. 232, 96-100. doi: 10.1006/bbrc.1997.6231
157. Underwood, C. R., Garibay, P., Knudsen, L. B., Hastrup, S., Peters, G. H., Rudolph, R., et al. (2010). Crystal structure of Glucagon-like Peptide-1 in complex with the extracellular domain of the Glucagon-like Peptide-1 receptor. J. Biol. Chem. 285, 723-730. doi: 10.1074/jbc. M109.033829
158. Unson, C. G., Wu, C.-R., Jiang, Y., Yoo, B., Cheung, C., Sakmar, T. P., et al. (2002). Roles of specific extracellular domains of the glucagon receptor in ligand binding and signaling. Biochemistry 41, 11795-11803. doi: 10.1021/bi025711j
159. Vilardaga, J. P., Bunemann, M., Krasel, C., Castro, M., and Lohse, M. J. (2003). Measurement of the millisecond activation switch of G protein-coupled receptors in living cells. Nat. Biotechnol. 21, 807-812. doi: 10.1038/nbt838
160. Vilardaga, J.-P., Romero, G., Friedman, P., and Gardella, T. (2011). Molecular basis of parathyroid hormone receptor signaling and trafficking: a family B GPCR paradigm. Cell. Mol. Life Sci. 68, 1-13. doi: 10.1007/s00018-010-0465-9
161. Vohra, S., Taddese, B., Conner, A. C., Poyner, D. R., Hay, D. L., Barwell, J., et al. (2013). Similarity between class A and class B G-protein-coupled receptors exemplified through calcitonin gene-related peptide receptor modelling and mutagenesis studies. J. R. Soc. Interface 10:20120846. doi: 10.1098/rsif.2012.0846
162. Wang, B., Ardura, J. A., Romero, G., Yang, Y. M., Hall, R. A., and Friedman, P. A. (2010). Na/H exchanger regulatory factors control parathyroid hormone receptor signaling by facilitating differential activation of g alpha protein subunits. J. Biol. Chem. 285, 26976-26986. doi: 10.1074/jbc. M110.147785
163. Warne, T., Moukhametzianov, R., Baker, J. G., Nehmé, R., Edwards, P. C., Leslie, A. G. W., et al. (2011). The structural basis for agonist and partial agonist action on a beta(1)-adrenergic receptor. Nature 469, 241-244. doi: 10.1038/nature09746
164. Watkins, H., Au, M., Bobby, R., Archbold, J., Abdul-Manan, N., Moore, J., et al. (2013). Identification of key residues involved in adrenomedullin binding to the AM1 receptor. Br. J. Pharmacol. 169, 143-155. doi: 10.1111/bph.12118
165. Wootten, D., Simms, J., Miller, L. J., Christopoulos, A., and Sexton, P. M. (2013). Polar transmembrane interactions drive formation of ligand-specific and signal pathway-biased family B G protein-coupled receptor conformations. Proc. Natl. Acad. Sci. U.S.A. 110, 5211-5216. doi: 10.1073/pnas.1221585110
166. Wright, D. E., and Rodbell, M. (1979). Glucagon1-6 binds to the glucagon receptor and activates hepatic adenylate cyclase. J. Biol. Chem. 254, 268-269.
167. Wu, B., Chien, E. Y., Mol, C. D., Fenalti, G., Liu, W., Katritch, V., et al. (2010). Structures of the CXCR4 chemokine GPCR with small-molecule and cyclic peptide antagonists. Science 330, 1066-1071. doi: 10.1126/science.1194396
168. Xiao, Q., Jeng, W., and Wheeler, M. B. (2000). Characterization of glucagon-like peptide-1 receptor-binding determinants. J. Mol. Endocrinol. 25, 321-335. doi: 10.1677/jme.0.0250321
169. Yamashita, T., Tose, K., and Shichida, Y. (2008). First cytoplasmic loop of Glucagon-like Peptide-1 receptor can function at the third cytoplasmic loop position of rhodopsin. Photochem. Photobiol. 84, 931-936. doi: 10.1111/j.1751-1097.2008.00327.x
170. Yao, X. J., Parnot, C., Deupi, X., Ratnala, V. R. P., Swaminath, G., Farrens, D., et al. (2006). Coupling ligand structure to specific conformational switches in the beta(2)-adrenoceptor. Nat. Chem. Biol. 2, 417-422. doi: 10.1038/nchembio801
171. Yao, X. J., Vélez Ruiz, G. V., Whorton, M. R., Rasmussen, S. G., Devree, B. T., Deupi, X., et al. (2009). The effect of ligand efficacy on the formation and stability of a GPCR-G protein complex. Proc. Natl. Acad. Sci. U.S.A. 106, 9501-9506. doi: 10.1073/pnas.0811437106
172. Yaqub, T., Tikhonova, I. G., Lattig, J., Magnan, R., Laval, M., Escrieut, C., et al. (2010). Identification of determinants of glucose-dependent insulinotropic polypeptide receptor that interact with N-terminal biologically active region of the natural ligand. Mol. Pharmacol. 77, 547-558. doi: 10.1124/mol.109.060111
173. Zhou, A. T., Bessalle, R., Bisello, A., Nakamoto, C., Rosenblatt, M., Suva, L. J., et al. (1997). Direct mapping of an agonist-binding domain within the parathyroid hormone/parathyroid hormone-related protein receptor by photoaffinity crosslinking. Proc. Natl. Acad. Sci. U.S.A. 94, 3644-3649. doi: 10.1073/pnas.94.8.3644
174. Zuckermann, R. N., and Kodadek, T. (2009). Peptoids as potential therapeutics. Curr. Opin. Mol. Ther. 11, 299-307.