The hinge region of human Thyroid-stimulating hormone (TSH) receptor operates as a tunable switch between hormone binding and receptor activation

PLoS ONE

Volumn 7, Issue 7, 2012, Pages

  Majumdar, Ritankar ^a   Dighe, Rajan R ^a  

^a INDIAN INSTITUTE OF SCIENCE   (India)

Author keywords

[No Author keywords available]

Indexed keywords

EPITOPE; MONOCLONAL ANTIBODY; MONOCLONAL ANTIBODY 311 62; MONOCLONAL ANTIBODY 311 87; THYROTROPIN; THYROTROPIN RECEPTOR; UNCLASSIFIED DRUG;

ANTIBODY AFFINITY; ANTIBODY SPECIFICITY; ANTIGEN BINDING; ARTICLE; BINDING SITE; CONFORMATIONAL TRANSITION; CONTROLLED STUDY; HINGE REGION; HORMONAL REGULATION; HORMONE BINDING; HORMONE PROTEIN COMPLEX; HUMAN; HUMAN CELL; MUTATIONAL ANALYSIS; PROTEIN CONFORMATION; PROTEIN DOMAIN; PROTEIN FUNCTION; PROTEIN INTERACTION; SIGNAL TRANSDUCTION; STRUCTURE ACTIVITY RELATION;

ALGORITHMS; ALLOSTERIC REGULATION; AMINO ACID MOTIFS; AMINO ACID SEQUENCE; AMINO ACID SUBSTITUTION; ANIMALS; ANTIBODIES, MONOCLONAL, MURINE-DERIVED; BINDING, COMPETITIVE; CATTLE; CELL SURFACE DISPLAY TECHNIQUES; CYCLIC AMP; EPITOPE MAPPING; HEK293 CELLS; HUMANS; MUTAGENESIS, SITE-DIRECTED; PEPTIDE FRAGMENTS; PROTEIN BINDING; PROTEIN STRUCTURE, TERTIARY; RECEPTORS, THYROTROPIN; SECOND MESSENGER SYSTEMS; THYROTROPIN;

EID: 84863639088     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0040291     Document Type: Article

References (66)

1. Fan Q, Hendrickson W, (2005) Structure of human follicle-stimulating hormone in complex with its receptor. Nature 433: 269-277.
2. Sanders J, Chirgadze DY, Sanders P, Baker S, Sullivan A, et al. (2007) Crystal structure of the TSH receptor in complex with a thyroid-stimulating autoantibody. Thyroid 17: 395-410.
3. Ji I, Lee C, Song Y, Conn PM, Ji TH, (2002) Cis- and Trans-Activation of Hormone Receptors: the LH Receptor. Mol Endocrinol 16: 1299-1308.
4. Lin W, Bernard MP, Cao D, Myers RV, Kerrigan JE, et al. (2007) Follitropin receptors contain cryptic ligand binding sites. Mol Cell Endocrinol 260-262: 83-92.
5. Mueller S, Kleinau G, Jaeschke H, Paschke R, Krause G, (2008) Extended Hormone Binding Site of the Human Thyroid Stimulating Hormone Receptor. Journal of Biological Chemistry 283: 18048-18055.
6. Zhang ML, Sugawa H, Kosugi S, Mori T, (1995) Constitutive activation of the thyrotropin receptor by deletion of a portion of the extracellular domain. Biochem Biophys Res Commun 211: 205-210.
7. Mueller S, Jaeschke H, Gunther R, Paschke R, (2010) The hinge region: an important receptor component for GPHR function. Trends Endocrinol Metab 21: 111-122.
8. Vlaeminck-Guillem V, Ho SC, Rodien P, Vassart G, Costagliola S, (2002) Activation of the cAMP pathway by the TSH receptor involves switching of the ectodomain from a tethered inverse agonist to an agonist. Mol Endocrinol 16: 736-746.
9. Mueller S, Kleinau G, Jaeschke H, Neumann S, Krause G, et al. (2006) Significance of Ectodomain Cysteine Boxes 2 and 3 for the Activation Mechanism of the Thyroid-stimulating Hormone Receptor. Journal of Biological Chemistry 281: 31638-31646.
10. Sangkuhl K, Schulz A, Schultz G, Schöneberg T, (2002) Structural Requirements for Mutational Lutropin/Choriogonadotropin Receptor Activation. Journal of Biological Chemistry 277: 47748-47755.
11. Vassart G, Pardo L, Costagliola S, (2004) A molecular dissection of the glycoprotein hormone receptors. Trends in Biochemical Sciences 29: 119-126.
12. Dighe RR, Murthy GS, Kurkalli BS, Moudgal NR, (1990) Conformation of the alpha-subunit of glycoprotein hormones: a study using polyclonal and monoclonal antibodies. Mol Cell Endocrinol 72: 63-70.
13. Agrawal G, Dighe RR, (2009) Critical Involvement of the Hinge Region of the Follicle-stimulating Hormone Receptor in the Activation of the Receptor. Journal of Biological Chemistry 284: 2636-2647.
14. Sanders J, Oda Y, Roberts S-A, Maruyama M, Furmaniak J, et al. (1997) Understanding the thyrotropin receptor function-structure relationship. Baillière's Clinical Endocrinology and Metabolism 11: 451-479.
15. Majumdar R, Saha S, Dighe RR, Chakravarty AR, (2010) Enhanced photodynamic effect of cobalt(iii) dipyridophenazine complex on thyrotropin receptor expressing HEK293 cells. Metallomics 2: 754-765.
16. Dighe RR, Murthy GS, Moudgal NR, (1990) Two simple and rapid methods to detect monoclonal antibodies with identical epitope specificities in a large population of monoclonal antibodies. J Immunol Methods 131: 229-236.
17. Dighe RR, Moudgal NR, (1983) Use of alpha- and beta-subunit specific antibodies in studying interaction of hCG with Leydig cell receptors. Arch Biochem Biophys 225: 490-499.
18. WANG W, Malcolm B, (1999) Two-stage PCR protocol allowing introduction of multiple mutations, deletions and insertions using QuikChange site-directed mutagenesis. Biotechniques 26: 680-682.
19. Fraker PJ, Speck JC Jr, (1978) Protein and cell membrane iodinations with a sparingly soluble chloroamide, 1,3,4,6-tetrachloro-3a,6a-diphrenylglycoluril. Biochem Biophys Res Commun 80: 849-857.
20. Rapoport B, Takai NA, Filetti S, (1982) Evidence for species specificity in the interaction between thyrotropin and thyroid-stimulating immunoglobulin and their receptor in thyroid tissue. J Clin Endocrinol Metab 54: 1059-1062.
21. Urizar E, Montanelli L, Loy T, Bonomi M, Swillens S, et al. (2005) Glycoprotein hormone receptors: link between receptor homodimerization and negative cooperativity. EMBO J 24: 1954-1964.
22. Guan R, Feng X, Wu X, Zhang M, Zhang X, et al. (2009) Bioluminescence Resonance Energy Transfer Studies Reveal Constitutive Dimerization of the Human Lutropin Receptor and a Lack of Correlation between Receptor Activation and the Propensity for Dimerization. Journal of Biological Chemistry 284: 7483-7494.
23. Nagayama Y, Wadsworth HL, Chazenbalk GD, Russo D, Seto P, et al. (1991) Thyrotropin-luteinizing hormone/chorionic gonadotropin receptor extracellular domain chimeras as probes for thyrotropin receptor function. Proc Natl Acad Sci U S A 88: 902-905.
24. Nagayama Y, Rapoport B, (1992) Role of the carboxyl-terminal half of the extracellular domain of the human thyrotropin receptor in signal transduction. Endocrinology 131: 548-552.
25. Kopp P, Muirhead S, Jourdain N, Gu WX, Jameson JL, et al. (1997) Congenital hyperthyroidism caused by a solitary toxic adenoma harboring a novel somatic mutation (serine281->isoleucine) in the extracellular domain of the thyrotropin receptor. The Journal of Clinical Investigation 100: 1634-1639.
26. Ho SC, Van Sande J, Lefort A, Vassart G, Costagliola S, (2001) Effects of mutations involving the highly conserved S281HCC motif in the extracellular domain of the thyrotropin (TSH) receptor on TSH binding and constitutive activity. Endocrinology 142: 2760-2767.
27. Nakabayashi K, Kudo M, Hsueh AJ, Maruo T, (2003) Activation of the luteinizing hormone receptor in the extracellular domain. Mol Cell Endocrinol 202: 139-144.
28. Chen CR, McLachlan SM, Rapoport B, (2008) Identification of key amino acid residues in a thyrotropin receptor monoclonal antibody epitope provides insight into its inverse agonist and antagonist properties. Endocrinology 149: 3427-3434.
29. Jaeschke H, Neumann S, Kleinau G, Mueller S, Claus M, et al. (2006) An aromatic environment in the vicinity of serine 281 is a structural requirement for thyrotropin receptor function. Endocrinology 147: 1753-1760.
30. Kleinau G, Jaeschke H, Mueller S, Raaka BM, Neumann S, et al. (2008) Evidence for cooperative signal triggering at the extracellular loops of the TSH receptor. FASEB J 22: 2798-2808.
31. Neumann S, Claus M, Paschke R, (2005) Interactions between the extracellular domain and the extracellular loops as well as the 6th transmembrane domain are necessary for TSH receptor activation. Eur J Endocrinol 152: 625-634.
32. Chen CR, McLachlan SM, Rapoport B, (2010) Thyrotropin (TSH) receptor residue E251 in the extracellular leucine-rich repeat domain is critical for linking TSH binding to receptor activation. Endocrinology 151: 1940-1947.
33. Nagayama Y, Wadsworth HL, Russo D, Chazenbalk GD, Rapoport B, (1991) Binding domains of stimulatory and inhibitory thyrotropin (TSH) receptor autoantibodies determined with chimeric TSH-lutropin/chorionic gonadotropin receptors. The Journal of Clinical Investigation 88: 336-340.
34. Zhang M, Tong KPT, Fremont V, Chen J, Narayan P, et al. (2000) The Extracellular Domain Suppresses Constitutive Activity of the Transmembrane Domain of the Human TSH Receptor: Implications for Hormone-Receptor Interaction and Antagonist Design. Endocrinology 141: 3514-3517.
35. Powell-Jones CH, Thomas CG Jr, Nayfeh SN, (1979) Contribution of negative cooperativity to the thyrotropin-receptor interaction in normal human thyroid: kinetic evaluation. Proc Natl Acad Sci U S A 76: 705-709.
36. Chen CR, McLachlan SM, Rapoport B, (2011) Evidence That the Thyroid-stimulating Hormone (TSH) Receptor Transmembrane Domain Influences Kinetics of TSH Binding to the Receptor Ectodomain. Journal of Biological Chemistry 286: 6219.
37. Smith BR, Sanders J, Furmaniak J, (2007) The TSH Receptor- A new Crystal Structure. Hot Thyroidology.
38. Kenakin T, (2005) New Concepts in Drug Discovery: Collateral Efficacy and Permissive Antagonism. Nat Rev Drug Discov 4: 919-927.
39. Price MR, Baillie GL, Thomas A, Stevenson LA, Easson M, et al. (2005) Allosteric Modulation of the Cannabinoid CB1 Receptor. Molecular Pharmacology 68: 1484-1495.
40. Kaumann A, Marano M, (1982) On equilibrium dissociation constants for complexes of drug-receptor subtypes. Naunyn-Schmiedeberg's Archives of Pharmacology 318: 192-201.
41. Strange PG, (2008) Agonist binding, agonist affinity and agonist efficacy at G protein-coupled receptors. Br J Pharmacol 153: 1353-1363.
42. Christopoulos A, Kenakin T, (2002) G Protein-Coupled Receptor Allosterism and Complexing. Pharmacological Reviews 54: 323-374.
43. Ehlert FJ, (1985) The relationship between muscarinic receptor occupancy and adenylate cyclase inhibition in the rabbit myocardium. Mol Pharmacol 28: 410-421.
44. Ways J, Parham P, (1983) The binding of monoclonal antibodies to cell-surface molecules. A quantitative analysis with immunoglobulin G against two alloantigenic determinants of the human transplantation antigen HLA-A2. Biochemical Journal 216: 423.
45. Schmidt A, MacColl R, Lindau-Shepard B, Buckler DR, Dias JA, (2001) Hormone-induced Conformational Change of the Purified Soluble Hormone Binding Domain of Follitropin Receptor Complexed with Single Chain Follitropin. Journal of Biological Chemistry 276: 23373-23381.
46. Demarest JF, Sparks SS, Schell K, Shibayama S, McDanal CB, et al. (2008) In Vitro and Clinical Investigation of the Relationship Between CCR5 Receptor Occupancy and Anti-HIV Activity of Aplaviroc. The Journal of Clinical Pharmacology 48: 1179-1188.
47. Gupta A, Décaillot FM, Gomes I, Tkalych O, Heimann AS, et al. (2007) Conformation State-sensitive Antibodies to G-protein-coupled Receptors. Journal of Biological Chemistry 282: 5116-5124.
48. Sánchez IE, Kiefhaber T, (2003) Non-linear rate-equilibrium free energy relationships and Hammond behavior in protein folding. Biophysical Chemistry 100: 397-407.
49. Kleinau G, Mueller S, Jaeschke H, Grzesik P, Neumann S, et al. (2011) Defining Structural and Functional Dimensions of the Extracellular Thyrotropin Receptor Region. Journal of Biological Chemistry 286: 22622-22631.
50. Núñez Miguel R, Sanders J, Chirgadze DY, Furmaniak J, Rees Smith B, (2009) Thyroid stimulating autoantibody M22 mimics TSH binding to the TSH receptor leucine rich domain: a comparative structural study of protein-protein interactions. Journal of Molecular Endocrinology 42: 381-395.
51. Costagliola S, Bonomi M, Morgenthaler NG, Van Durme J, Panneels V, et al. (2004) Delineation of the Discontinuous-Conformational Epitope of a Monoclonal Antibody Displaying Full in Vitro and in Vivo Thyrotropin Activity. Molecular Endocrinology 18: 3020-3034.
52. Sanders J, Jeffreys J, Depraetere H, Evans M, Richards T, et al. (2004) Characteristics of a human monoclonal autoantibody to the thyrotropin receptor: sequence structure and function. Thyroid 14: 560-570.
53. Mizutori Y, Chen C-R, Latrofa F, McLachlan SM, Rapoport B, (2009) Evidence that Shed Thyrotropin Receptor A Subunits Drive Affinity Maturation of Autoantibodies Causing Graves' Disease. Journal of Clinical Endocrinology & Metabolism 94: 927-935.
54. Costagliola S, Franssen J, Bonomi M, Urizar E, Willnich M, et al. (2002) Generation of a mouse monoclonal TSH receptor antibody with stimulating activity* 1. Biochemical and biophysical research communications 299: 891-896.
55. Nurwakagari P, Breit A, Hess C, Salman-Livny H, Ben-Menahem D, et al. (2007) A conformational contribution of the luteinizing hormone-receptor ectodomain to receptor activation. J Mol Endocrinol 38: 259-275.
56. Roth KE, Dias JA, (1996) Follitropin Conformational Stability Mediated by Loop 2β Effects Follitropin-Receptor Interaction†. Biochemistry 35: 7928-7935.
57. Pantel J, Remy JJ, Salesse R, Jolivet A, Bidart JM, (1993) Unmasking of an immunoreactive site on the alpha subunit of human choriogonadotropin bound to the extracellular domain of its receptor. Biochem Biophys Res Commun 195: 588-593.
58. Mueller S, Kleinau G, Szkudlinski MW, Jaeschke H, Krause G, et al. (2009) The superagonistic activity of bovine thyroid-stimulating hormone (TSH) and the human TR1401 TSH analog is determined by specific amino acids in the hinge region of the human TSH receptor. J Biol Chem 284: 16317-16324.
59. Mizutori Y, Chen C, McLachlan S, Rapoport B, (2008) The thyrotropin receptor hinge region is not simply a scaffold for the leucine-rich domain but contributes to ligand binding and signal transduction. Molecular Endocrinology 22: 1171.
60. Shepherd PS, Da Costa CR, Cridland JC, Gilmore KS, Johnstone AP, (1999) Identification of an important thyrotrophin binding site on the human thyrotrophin receptor using monoclonal antibodies. Molecular and Cellular Endocrinology 149: 197-206.
61. Nicholson LB, Vlase H, Graves P, Nilsson M, Molne J, et al. (1996) Monoclonal antibodies to the human TSH receptor: epitope mapping and binding to the native receptor on the basolateral plasma membrane of thyroid follicular cells. Journal of Molecular Endocrinology 16: 159-170.
62. Ando T, Latif R, Pritsker A, Moran T, Nagayama Y, et al. (2002) A monoclonal thyroid-stimulating antibody. Journal of Clinical Investigation 110: 1667-1674.
63. Jeffreys J, Depraetere H, Sanders J, Oda Y, Evans M, et al. (2002) Characterization of the Thyrotropin Binding Pocket. Thyroid 12: 1051-1061.
64. Ando T, Latif R, Daniel S, Eguchi K, Davies TF, (2004) Dissecting Linear and Conformational Epitopes on the Native Thyrotropin Receptor. Endocrinology 145: 5185-5193.
65. Davies TF, Ando T, Lin RY, Tomer Y, Latif R, (2005) Thyrotropin receptor-associated diseases: from adenomata to Graves disease. J Clin Invest 115: 1972-1983.
66. Chen C-R, Salazar LM, McLachlan SM, Rapoport B, (2012) Novel Information on the Epitope of an Inverse Agonist Monoclonal Antibody Provides Insight into the Structure of the TSH Receptor. PLoS ONE 7: e31973.