Glucagon-like peptide-1 receptor dimerization differentially regulates agonist signaling but does not affect small molecule allostery

Proceedings of the National Academy of Sciences of the United States of America

Volumn 109, Issue 45, 2012, Pages 18607-18612

  Harikumar, Kaleeckal G ^a   Wootten, Denise ^b   Pinon, Delia I ^a   Koole, Cassandra ^b   Ball, Alicja M ^a   Furness, Sebastian G B ^b   Graham, Bim ^b   Dong, Maoqing ^a   Christopoulos, Arthur ^b   Miller, Laurence J ^a   Sexton, Patrick M ^b  

^a MAYO GRADUATE SCHOOL   (United States)

^b MONASH UNIVERSITY   (Australia)

Author keywords

Allosteric modulation; Biased signaling; Family B GPCRs; G protein coupled receptors

Indexed keywords

CALCIUM ION; CIS ACTING ELEMENT; CYCLIC AMP; GLUCAGON LIKE PEPTIDE 1 [7-36] AMIDE; GLUCAGON LIKE PEPTIDE 1 RECEPTOR; GUANINE NUCLEOTIDE BINDING PROTEIN; HOMODIMER; LIGAND; MEMBRANE PROTEIN; MITOGEN ACTIVATED PROTEIN KINASE 1; MITOGEN ACTIVATED PROTEIN KINASE 3; OXYNTOMODULIN; TRANSMEMBRANE HELIX 4 PROTEIN; UNCLASSIFIED DRUG;

ALLOSTERISM; ARTICLE; BINDING AFFINITY; BIOLUMINESCENCE RESONANCE ENERGY TRANSFER; CALCIUM CELL LEVEL; CALCIUM MOBILIZATION; CELL LINE; CONCENTRATION RESPONSE; CONTROLLED STUDY; DIMERIZATION; DRUG DESIGN; ENZYME PHOSPHORYLATION; GENE MUTATION; PRIORITY JOURNAL; PROMOTER REGION; PROTEIN BINDING; PROTEIN PROTEIN INTERACTION; SIGNAL TRANSDUCTION;

ALLOSTERIC REGULATION; ANIMALS; CERCOPITHECUS AETHIOPS; CHO CELLS; COS CELLS; CRICETINAE; CYCLIC AMP; HUMANS; PEPTIDES; PROTEIN MULTIMERIZATION; PROTEIN SUBUNITS; RECEPTORS, GLUCAGON; SIGNAL TRANSDUCTION; SMALL MOLECULE LIBRARIES;

EID: 84868585481     PISSN: 00278424     EISSN: 10916490     Source Type: Journal    
DOI: 10.1073/pnas.1205227109     Document Type: Article

References (46)

1. Christopoulos A (2002) Allosteric binding sites on cell-surface receptors: Novel targets for drug discovery. Nat Rev Drug Discov 1(3):198-210.
2. Casadó V, et al. (2009) GPCR homomers and heteromers: A better choice as targets for drug development than GPCR monomers? Pharmacol Ther 124(2):248-257.
3. Milligan G (2009) G protein-coupled receptor hetero-dimerization: Contribution to pharmacology and function. Br J Pharmacol 158(1):5-14.
4. Kniazeff J, Prézeau L, Rondard P, Pin JP, Goudet C (2011) Dimers and beyond: The functional puzzles of class C GPCRs. Pharmacol Ther 130(1):9-25.
5. 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. (Pubitemid 47093370)
6. Whorton MR, et al. (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. (Pubitemid 47185966)
7. 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.
8. Albizu L, et al. (2010) Time-resolved FRET between GPCR ligands reveals oligomers in native tissues. Nat Chem Biol 6(8):587-594.
9. Pin JP, et al. (2007) International Union of Basic and Clinical Pharmacology. LXVII. Recommendations for the recognition and nomenclature of G protein-coupled receptor heteromultimers. Pharmacol Rev 59(1):5-13.
10. Ferré S, et al. (2009) Building a new conceptual framework for receptor heteromers. Nat Chem Biol 5(3):131-134.
11. Khelashvili G, et al. (2010) GPCR-OKB: The G protein coupled receptor oligomer knowledge base. Bioinformatics 26(14):1804-1805.
12. Hern JA, et al. (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.
13. Lambert NA (2010) GPCR dimers fall apart. Sci Signal 3(115):pe12.
14. Fonseca JM, Lambert NA (2009) Instability of a class a G protein-coupled receptor oligomer interface. Mol Pharmacol 75(6):1296-1299.
15. Kasai RS, et al. (2011) Full characterization of GPCR monomer-dimer dynamic equilibrium by single molecule imaging. J Cell Biol 192(3):463-480.
16. Fung JJ, et al. (2009) Ligand-regulated oligomerization of beta(2)-adrenoceptors in a model lipid bilayer. EMBO J 28(21):3315-3328.
17. Harikumar KG, Ball AM, Sexton PM, Miller LJ (2010) Importance of lipid-exposed residues in transmembrane segment four for family B calcitonin receptor homo-dimerization. Regul Pept 164(2-3):113-119.
18. Harikumar KG, Pinon DI, Miller LJ (2007) Transmembrane segment IV contributes a functionally important interface for oligomerization of the Class II G protein-coupled secretin receptor. J Biol Chem 282(42):30363-30372. (Pubitemid 350035177)
19. Harikumar KG, Happs RM, Miller LJ (2008) Dimerization in the absence of higher-order oligomerization of the G protein-coupled secretin receptor. Biochim Biophys Acta 1778(11):2555-2563.
20. Héroux M, Hogue M, Lemieux S, Bouvier M (2007) Functional calcitonin gene-related peptide receptors are formed by the asymmetric assembly of a calcitonin receptor-like receptor homo-oligomer and a monomer of receptor activity-modifying protein-1. J Biol Chem 282(43):31610-31620. (Pubitemid 350044900)
21. Kraetke O, et al. (2005) Dimerization of corticotropin-releasing factor receptor type 1 is not coupled to ligand binding. J Recept Signal Transduct Res 25(4- 6):251-276.
22. Langer I, Gaspard N, Robberecht P (2006) Pharmacological properties of Chinese hamster ovary cells coexpressing two vasoactive intestinal peptide receptors (hVPAC1 and hVPAC2). Br J Pharmacol 148(8):1051-1059. (Pubitemid 44223010)
23. Pioszak AA, Harikumar KG, Parker NR, Miller LJ, Xu HE (2010) Dimeric arrangement of the parathyroid hormone receptor and a structural mechanism for ligand-induced dissociation. J Biol Chem 285(16):12435-12444.
24. Seck T, Baron R, Horne WC (2003) The alternatively spliced deltae13 transcript of the rabbit calcitonin receptor dimerizes with the C1a isoform and inhibits its surface expression. J Biol Chem 278(25):23085-23093. (Pubitemid 36830374)
25. Harikumar KG, Morfis MM, Lisenbee CS, Sexton PM, Miller LJ (2006) Constitutive formation of oligomeric complexes between family B G protein-coupled vasoactive intestinal polypeptide and secretin receptors. Mol Pharmacol 69(1):363-373. (Pubitemid 43048923)
26. Harikumar KG, Morfis MM, Sexton PM, Miller LJ (2008) Pattern of intra-family hetero-oligomerization involving the G-protein-coupled secretin receptor. J Mol Neurosci 36 (1-3):279-285.
27. Schelshorn D, et al. (2012) Lateral allosterism in the glucagon receptor family: Glucagon- like peptide 1 induces G-protein-coupled receptor heteromer formation. Mol Pharmacol 81(3):309-318.
28. May LT, Leach K, Sexton PM, Christopoulos A (2007) Allosteric modulation of G protein-coupled receptors. Annu Rev Pharmacol Toxicol 47:1-51. (Pubitemid 46277033)
29. Hoare SR (2007) Allosteric modulators of class B G-protein-coupled receptors. Curr Neuropharmacol 5(3):168-179.
30. Knudsen LB, et al. (2007) Small-molecule agonists for the glucagon-like peptide 1 receptor. Proc Natl Acad Sci USA 104(3):937-942. (Pubitemid 46154715)
31. Gao F, et al. (2009) Functional importance of a structurally distinct homodimeric complex of the family B G protein-coupled secretin receptor. Mol Pharmacol 76(2): 264-274.
32. Alexander SPH, Mathie A, Peters JA (2011) Guide to Receptors and Channels (GRAC), 5th Ed. Br J Pharmacol 164(Suppl 1):S1-S324.
33. Baggio LL, Drucker DJ (2007) Biology of incretins: GLP-1 and GIP. Gastroenterology 132(6):2131-2157. (Pubitemid 46711096)
34. Koole C, et al. (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(3):456 -465.
35. Lovshin JA, Drucker DJ (2009) Incretin-based therapies for type 2 diabetes mellitus. Nat Rev Endocrinol 5(5):262-269.
36. Wootten D, et al. (2012) Allosteric modulation of endogenous metabolites as an avenue for drug discovery. Mol Pharmacol 82(2):281-290.
37. Sonoda N, et al. (2008) Beta-Arrestin-1 mediates glucagon-like peptide-1 signaling to insulin secretion in cultured pancreatic beta cells. Proc Natl Acad Sci USA 105(18):6614-6619. (Pubitemid 351754555)
38. Koole C, et al. (2012) 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(6):3659-3673.
39. Koole C, et al. (2011) Polymorphism and ligand dependent changes in human glu-cagon- like peptide-1 receptor (GLP-1R) function: Allosteric rescue of loss of function mutation. Mol Pharmacol 80(3):486-497.
40. Sloop KW, et al. (2010) Novel small molecule glucagon-like peptide-1 receptor agonist stimulates insulin secretion in rodents and from human islets. Diabetes 59(12): 3099-3107.
41. Guo W, et al. (2008) Dopamine D2 receptors form higher order oligomers at physiological expression levels. EMBO J 27(17):2293-2304.
42. Guo W, Shi L, Filizola M, Weinstein H, Javitch JA (2005) Crosstalk in G protein-coupled receptors: Changes at the transmembrane homodimer interface determine activation. Proc Natl Acad Sci USA 102(48):17495-17500. (Pubitemid 41740894)
43. Guo W, Shi L, Javitch JA (2003) The fourth transmembrane segment forms the interface of the dopamine D2 receptor homodimer. J Biol Chem 278(7):4385-4388. (Pubitemid 36800928)
44. Ziegler N, Bätz J, Zabel U, Lohse MJ, Hoffmann C (2011) FRET-based sensors for the human M1-, M3-, and M5-acetylcholine receptors. Bioorg Med Chem 19(3):1048-1054.
45. Ambrosio M, Lohse MJ (2012) Nonequilibrium activation of a G-protein-coupled receptor. Mol Pharmacol 81(6):770-777.
46. Dong M, Gao F, Pinon DI, Miller LJ (2008) Insights into the structural basis of endogenous agonist activation of family B G protein-coupled receptors. Mol Endocrinol 22(6):1489-1499. (Pubitemid 351787007)