Differential impact of amino acid substitutions on critical residues of the human glucagon-like peptide-1 receptor involved in peptide activity and small-molecule allosterys

Journal of Pharmacology and Experimental Therapeutics

Volumn 353, Issue 1, 2015, Pages 52-63

  Koole, Cassandra ^a   Wootten, Denise ^a   Simms, John ^a,c   Miller, Laurence J ^b   Christopoulos, Arthur ^a   Sexton, Patrick M ^a  

^a MONASH UNIVERSITY   (Australia)

^b MAYO GRADUATE SCHOOL   (United States)

^c ASTON UNIVERSITY   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

ADENYLATE CYCLASE; GLUCAGON LIKE PEPTIDE 1 RECEPTOR; PEPTIDE; CALCIUM; CYCLIC AMP; EXENDIN (9-39); GLUCAGON LIKE PEPTIDE 1; GLUCAGON RECEPTOR; GLUCAGON-LIKE PEPTIDE-1 RECEPTOR; MITOGEN ACTIVATED PROTEIN KINASE 1; MITOGEN ACTIVATED PROTEIN KINASE 3; PEPTIDE FRAGMENT;

ALLOSTERISM; AMINO ACID SUBSTITUTION; ANIMAL CELL; ARTICLE; BINDING AFFINITY; BIOACCUMULATION; CELL SURFACE; CONTROLLED STUDY; CRYSTAL STRUCTURE; ENZYME ACTIVITY; HOMOZYGOSITY; LIGAND BINDING; NONHUMAN; PRIORITY JOURNAL; PROTEIN BINDING; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; PROTEIN POLYMORPHISM; SIGNAL TRANSDUCTION; SINGLE NUCLEOTIDE POLYMORPHISM; SITE DIRECTED MUTAGENESIS; AGONISTS; ANIMAL; ANTAGONISTS AND INHIBITORS; CHO CELL LINE; CRICETULUS; EXTRACELLULAR SPACE; GENETICS; HUMAN; METABOLISM; MUTATION; PHOSPHORYLATION;

ALLOSTERIC REGULATION; AMINO ACID SUBSTITUTION; ANIMALS; CALCIUM; CHO CELLS; CRICETULUS; CYCLIC AMP; EXTRACELLULAR SPACE; GLUCAGON-LIKE PEPTIDE 1; HUMANS; MITOGEN-ACTIVATED PROTEIN KINASE 1; MITOGEN-ACTIVATED PROTEIN KINASE 3; MUTATION; PEPTIDE FRAGMENTS; PHOSPHORYLATION; POLYMORPHISM, SINGLE NUCLEOTIDE; RECEPTORS, GLUCAGON; SIGNAL TRANSDUCTION;

EID: 84923340465     PISSN: 00223565     EISSN: 15210103     Source Type: Journal    
DOI: 10.1124/jpet.114.220913     Document Type: Article

References (62)

1. Abad C, Gomariz RP, and Waschek JA (2006) Neuropeptide mimetics and antagonists in the treatment of inflammatory disease: focus on VIP and PACAP. Curr Top Med Chem 6:151-163.
2. Adeghate E and Kalász H (2011) Amylin analogues in the treatment of diabetes mellitus: medicinal chemistry and structural basis of its function. Open Med Chem J 5(Suppl 2):78-81.
3. Al-Sabah S and Donnelly D (2003) The positive charge at Lys-288 of the glucagon-like peptide-1 (GLP-1) receptor is important for binding the N-terminus of peptide agonists. FEBS Lett 553:342-346.
4. Baggio LL and Drucker DJ (2007) Biology of incretins: GLP-1 and GIP. Gastroenterology 132:2131-2157.
5. Bavec A, Hällbrink 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.
6. Beinborn M, Worrall CI, McBride EW, and Kopin AS (2005) A human glucagon-like peptide-1 receptor polymorphism results in reduced agonist responsiveness. Regul Pept 130:1-6.
7. Black JW and Leff P (1983) Operational models of pharmacological agonism. Proc R Soc Lond B Biol Sci 220:141-162.
8. Brenneman DE (2007) Neuroprotection: a comparative view of vasoactive intestinal peptide and pituitary adenylate cyclase-activating polypeptide. Peptides 28:1720-1726.
9. Brubaker PL (2007) Incretin-based therapies: mimetics versus protease inhibitors. Trends Endocrinol Metab 18:240-245.
10. Chen Q, Pinon DI, Miller LJ, 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.
11. Chen Q, Pinon DI, Miller LJ, and Dong M (2010) Spatial approximations between residues 6 and 12 in the amino-terminal region of glucagon-like peptide 1 and its receptor: a region critical for biological activity. J Biol Chem 285:24508-24518.
12. Cheng Y and Prusoff WH (1973) Relationship between the inhibition constant (K1) and the concentration of inhibitor which causes 50 per cent inhibition (I50) of an enzymatic reaction. Biochem Pharmacol 22:3099-3108.
13. Coin I, Katritch V, Sun T, Xiang Z, Siu FY, Beyermann M, Stevens RC, and Wang L (2013) Genetically encoded chemical probes in cells reveal the binding path of urocortin-I to CRF class B GPCR. Cell 155:1258-1269.
14. Coopman K, Wallis R, Robb G, Brown AJ, Wilkinson GF, Timms D, and Willars GB (2011) Residues within the transmembrane domain of the glucagon-like peptide-1 receptor involved in ligand binding and receptor activation: modelling the ligandbound receptor. Mol Endocrinol 25:1804-1818.
15. Dong M, Lam PC, Gao F, Hosohata K, Pinon DI, Sexton PM, Abagyan R, and Miller LJ (2007) Molecular approximations between residues 21 and 23 of secretin and its receptor: development of a model for peptide docking with the amino terminus of the secretin receptor. Mol Pharmacol 72:280-290.
16. Dong M, Lam PC, Pinon DI, Hosohata K, Orry A, Sexton PM, Abagyan R, and Miller LJ (2011) Molecular basis of secretin docking to its intact receptor using multiple photolabile probes distributed throughout the pharmacophore. J Biol Chem 286:23888-23899.
17. Dong M, Li Z, Pinon DI, Lybrand TP, and Miller LJ (2004) Spatial approximation between the amino terminus of a peptide agonist and the top of the sixth transmembrane segment of the secretin receptor. J Biol Chem 279:2894-2903.
18. Estall JL and Drucker DJ (2006) Glucagon and glucagon-like peptide receptors as drug targets. Curr Pharm Des 12:1731-1750.
19. Fehmann HC and Habener JF (1992) Insulinotropic hormone glucagon-like peptide-I (7-37) stimulation of proinsulin gene expression and proinsulin biosynthesis in insulinoma beta TC-1 cells. Endocrinology 130:159-166.
20. Fortin JP, Schroeder JC, Zhu Y, Beinborn M, and Kopin AS (2010) Pharmacological characterization of human incretin receptor missense variants. J Pharmacol Exp Ther 332:274-280.
21. Gilligan PJ and Li YW (2004) Corticotropin-releasing factor antagonists: recent advances and exciting prospects for the treatment of human diseases. Curr Opin Drug Discov Devel 7:487-497.
22. Hager J, Hansen L, Vaisse C, Vionnet N, Philippi A, Poller W, Velho G, Carcassi C, Contu L, Julier C, et al. (1995) A missense mutation in the glucagon receptor gene is associated with non-insulin-dependent diabetes mellitus. Nat Genet 9:299-304.
23. Hällbrink M, Holmqvist T, Olsson M, Ostenson CG, 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.
24. Heller RS, Kieffer TJ, and Habener JF (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.
25. Hollenstein K, Kean J, Bortolato A, Cheng RK, Doré AS, Jazayeri A, Cooke RM, Weir M, and Marshall FH (2013) Structure of class B GPCR corticotropin-releasing factor receptor 1. Nature 499:438-443.
26. Holst B, Hastrup H, Raffetseder U, Martini L, and Schwartz TW (2001) Two active molecular phenotypes of the tachykinin NK1 receptor revealed by G-protein fusions and mutagenesis. J Biol Chem 276:19793-19799.
27. Hornby PJ and Moore BA (2011) The therapeutic potential of targeting the glucagonlike peptide-2 receptor in gastrointestinal disease. Expert Opin Ther Targets 15:637-646.
28. Jorgensen R, Kubale V, Vrecl M, Schwartz TW, and Elling CE (2007) Oxyntomodulin differentially affects glucagon-like peptide-1 receptor beta-arrestin recruitment and signaling through Galpha (s). J Pharmacol Exp Ther 322:148-154.
29. Jorgensen R, Martini L, Schwartz TW, and Elling CE (2005) Characterization of glucagon-like peptide-1 receptor beta-arrestin 2 interaction: a high-affinity receptor phenotype. Mol Endocrinol 19:812-823.
30. Kenakin T (1995) Agonist-receptor efficacy. II. Agonist trafficking of receptor signals. Trends Pharmacol Sci 16:232-238.
31. Kenakin T (2011) Functional selectivity and biased receptor signaling. J Pharmacol Exp Ther 336:296-302.
32. Koole C, Wootten D, Simms J, Miller LJ, Christopoulos A, and Sexton PM (2012a) 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.
33. Koole C, Wootten D, Simms J, Savage EE, Miller LJ, Christopoulos A, and Sexton PM (2012b) Second extracellular loop of human glucagon-like peptide-1 receptor (GLP-1R) differentially regulates orthosteric but not allosteric agonist binding and function. J Biol Chem 287:3659-3673.
34. Koole C, Wootten D, Simms J, Valant C, Miller LJ, Christopoulos A, and Sexton PM (2011) Polymorphism and ligand dependent changes in human glucagon-like peptide-1 receptor (GLP-1R) function: allosteric rescue of loss of function mutation. Mol Pharmacol 80:486-497.
35. Koole C, Wootten D, Simms J, Valant C, Sridhar R, Woodman OL, Miller LJ, Summers RJ, Christopoulos A, and Sexton PM (2010) Allosteric ligands of the glucagon-like peptide 1 receptor (GLP-1R) differentially modulate endogenous and exogenous peptide responses in a pathway-selective manner: implications for drug screening. Mol Pharmacol 78:456-465.
36. Leff P, Scaramellini C, Law C, and McKechnie K (1997) A three-state receptor model of agonist action. Trends Pharmacol Sci 18:355-362.
37. Lopez de Maturana R and Donnelly D (2002) The glucagon-like peptide-1 receptor binding site for the N-terminus of GLP-1 requires polarity at Asp198 rather than negative charge. FEBS Lett 530:244-248.
38. Lopez de Maturana R, Treece-Birch J, Abidi F, Findlay JB, and Donnelly D (2004) Met-204 and Tyr-205 are together important for binding GLP-1 receptor agonists but not their N-terminally truncated analogues. Protein Pept Lett 11:15-22.
39. Lu M, Wheeler MB, Leng XH, and Boyd AE, 3rd (1993) The role of the free cytosolic calcium level in beta-cell signal transduction by gastric inhibitory polypeptide and glucagon-like peptide I (7-37). Endocrinology 132:94-100.
40. Mathi SK, Chan Y, Li X, and Wheeler MB (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.
41. May LT, Avlani VA, Langmead CJ, Herdon HJ, Wood MD, Sexton PM, and Christopoulos A (2007) Structure-function studies of allosteric agonism at M2 muscarinic acetylcholine receptors. Mol Pharmacol 72:463-476.
42. McPherson J, Rivero G, Baptist M, Llorente J, Al-Sabah S, Krasel C, Dewey WL, Bailey CP, Rosethorne EM, Charlton SJ, et al. (2010) m-Opioid receptors: correlation of agonist efficacy for signalling with ability to activate internalization. Mol Pharmacol 78:756-766.
43. Miller LJ, Chen Q, Lam PC, Pinon DI, Sexton PM, Abagyan R, and Dong M (2011) Refinement of glucagon-like peptide 1 docking to its intact receptor using midregion photolabile probes and molecular modeling. J Biol Chem 286:15895-15907.
44. Montrose-Rafizadeh C, Avdonin P, Garant MJ, Rodgers BD, Kole S, Yang H, Levine MA, Schwindinger W, and Bernier M (1999) Pancreatic glucagon-like peptide-1 receptor couples to multiple G proteins and activates mitogen-activated protein kinase pathways in Chinese hamster ovary cells. Endocrinology 140:1132-1140.
45. Mulder JE, Kolatkar NS, and LeBoff MS (2006) Drug insight: Existing and emerging therapies for osteoporosis. Nat Clin Pract Endocrinol Metab 2:670-680.
46. Nijmeijer S, Vischer HF, Rosethorne EM, Charlton SJ, and Leurs R (2012) Analysis of multiple histamine H. receptor compound classes uncovers Gai protein- and b-arrestin2-biased ligands. Mol Pharmacol 82:1174-1182.
47. Nolte WM, Fortin JP, Stevens BD, Aspnes GE, Griffith DA, Hoth LR, Ruggeri RB, Mathiowetz AM, Limberakis C, Hepworth D, et al. (2014) A potentiator of orthosteric ligand activity at GLP-1R acts via covalent modification. Nat Chem Biol 10:629-631.
48. Sadee W, Hoeg E, Lucas J, and Wang D (2001) Genetic variations in human G protein-coupled receptors: implications for drug therapy. AAPS PharmSci 3:E22.
49. Salapatek AM, MacDonald PE, Gaisano HY, and Wheeler MB (1999) Mutations to the third cytoplasmic domain of the glucagon-like peptide 1 (GLP-1) receptor can functionally uncouple GLP-1-stimulated insulin secretion in HIT-T15 cells. Mol Endocrinol 13:1305-1317.
50. Schipani E, Langman C, Hunzelman J, Le Merrer M, Loke KY, Dillon MJ, Silve C, and Juppner H (1999) A novel parathyroid hormone (PTH)/PTH-related peptide receptor mutation in Jansen's metaphyseal chondrodysplasia. J Clin Endocrinol Metab 84:3052-3057.
51. Siani A, Iacone R, Russo O, Barba G, Russo P, Cappuccio FP, Galletti F, and Strazzullo P (2001) Gly40Ser polymorphism of the glucagon receptor gene is associated with central adiposity in men. Obes Res 9:722-726.
52. Siu FY, He M, de Graaf C, Han GW, Yang D, Zhang Z, Zhou C, Xu Q, Wacker D, Joseph JS, et al. (2013) Structure of the human glucagon class B G-protein-coupled receptor. Nature 499:444-449.
53. Sonoda N, Imamura T, Yoshizaki T, Babendure JL, Lu JC, and Olefsky JM (2008) Beta-arrestin-1 mediates glucagon-like peptide-1 signaling to insulin secretion in cultured pancreatic beta cells. Proc Natl Acad Sci USA 105:6614-6619.
54. Strachan RT, Sciaky N, Cronan MR, Kroeze WK, and Roth BL (2010) Genetic deletion of p90 ribosomal S6 kinase 2 alters patterns of 5-hydroxytryptamine 2A serotonin receptor functional selectivity. Mol Pharmacol 77:327-338.
55. Taboulet J, Frenkian M, Frendo JL, Feingold N, Jullienne A, and de Vernejoul MC (1998) Calcitonin receptor polymorphism is associated with a decreased fracture risk in post-menopausal women. Hum Mol Genet 7:2129-2133.
56. Takhar S, Gyomorey S, Su RC, Mathi SK, Li X, and Wheeler MB (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.
57. Tang CM and Insel PA (2005) Genetic variation in G-protein-coupled receptors. consequences for G-protein-coupled receptors as drug targets. Expert Opin Ther Targets 9:1247-1265.
58. Teng M, Johnson MD, Thomas C, Kiel D, Lakis JN, Kercher T, Aytes S, Kostrowicki J, Bhumralkar D, Truesdale L, et al. (2007) Small molecule ago-allosteric modulators of the human glucagon-like peptide-1 (hGLP-1) receptor. Bioorg Med Chem Lett 17:5472-5478.
59. Tokuyama Y, Matsui K, Egashira T, Nozaki O, Ishizuka T, and Kanatsuka A (2004) Five missense mutations in glucagon-like peptide 1 receptor gene in Japanese population. Diabetes Res Clin Pract 66:63-69.
60. Werry TD, Gregory KJ, Sexton PM, and Christopoulos A (2005) Characterization of serotonin 5-HT2C receptor signaling to extracellular signal-regulated kinases 1 and 2. J Neurochem 93:1603-1615.
61. Wootten D, Simms J, Miller LJ, Christopoulos A, and Sexton PM (2013) Polar transmembrane interactions drive formation of ligand-specific and signal pathwaybiased family B G protein-coupled receptor conformations. Proc Natl Acad Sci USA 110:5211-5216.
62. Zheng H, Chu J, Qiu Y, Loh HH, and Law PY (2008) Agonist-selective signaling is determined by the receptor location within the membrane domains. Proc Natl Acad Sci USA 105:9421-9426.