Signaling-sensitive amino acids surround the allosteric ligand binding site of the thyrotropin receptor

FASEB Journal

Volumn 24, Issue 7, 2010, Pages 2347-2354

  Kleinau, Gunnar ^a   Haas, Ann Karin ^a   Neumann, Susanne ^b   Worth, Catherine L ^a   Hoyer, Inna ^a   Furkert, Jens ^a   Rutz, Claudia ^a   Gershengorn, Marvin C ^b   Schülein, Ralf ^a   Krause, Gerd ^a  

^a LEIBNIZ INSTITUT FÜR MOLEKULARE PHARMAKOLOGIE   (Germany)

^b NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES   (United States)

Author keywords

Activation mechanisms; Allosteric small molecules; Constitutively activating mutations; Glycoprotein hormone receptors

Indexed keywords

CYCLIC AMP; THYROTROPIN RECEPTOR;

ALLOSTERISM; AMINO ACID SEQUENCE; ARTICLE; BINDING SITE; CELL STRAIN HEK293; CONTROLLED STUDY; HORMONE RECEPTOR INTERACTION; HUMAN; HUMAN CELL; LIGAND BINDING; MOLECULAR MODEL; PRIORITY JOURNAL; SIGNAL TRANSDUCTION; SITE DIRECTED MUTAGENESIS; STRUCTURE ACTIVITY RELATION;

ALLOSTERIC SITE; AMINO ACIDS; CYCLIC AMP; LIGANDS; MUTAGENESIS, SITE-DIRECTED; MUTATION, MISSENSE; RECEPTORS, THYROTROPIN; SIGNAL TRANSDUCTION;

EID: 77954455011     PISSN: 08926638     EISSN: 15306860     Source Type: Journal    
DOI: 10.1096/fj.09-149146     Document Type: Article

References (36)

1. Vassart, G., Pardo, L., and Costagliola, S. (2004) A molecular dissection of the glycoprotein hormone receptors. Trends Biochem. Sci. 29, 119-126
2. Themmen, A. P. N., and Huhtaniemi, I. T. (2000) Mutations of gonadotropins and gonadotropin receptors: elucidating the physiology and pathophysiology of pituitary-gonadal function. Endocr. Rev. 21, 551-583
3. Szkudlinski, M. W., Fremont, V., Ronin, C., and Weintraub, B. D. (2002) Thyroid-stimulating hormone and thyroid-stimulating hormone receptor structure-function relationships. Physiol. Rev. 82, 473-502
4. Simoni, M., Gromoll, J., and Nieschlag, E. (1997) The follicle-stimulating hormone receptor: biochemistry, molecular biology, physiology, and pathophysiology. Endocr. Rev. 18, 739-773
5. Schoneberg, T., Schulz, A., Biebermann, H., Hermsdorf, T., Rompler, H., and Sangkuhl, K. (2004) Mutant G-protein-coupled receptors as a cause of human diseases. Pharmacol. Ther. 104, 173-206
6. Kosugi, S., Sugawa, H., and Mori, T. (1996) TSH receptor and LH receptor, 1996. Endocr. J. 43, 595-604
7. Ascoli, M., Fanelli, F., and Segaloff, D. L. (2002) The lutropin/ choriogonadotropin receptor, a 2002 perspective. Endocr. Rev. 23, 141-174
8. Kleinau, G., and Krause, G. (2009) Thyrotropin and homologous glycoprotein hormone receptors: structural and functional aspects of extracellular signaling mechanisms. Endocr. Rev. 30, 133-151
9. Jaschke, H., Neumann, S., Moore, S., Thomas, C. J., Colson, A. O., Costanzi, S., Kleinau, G., Jiang, J. K., Paschke, R., Raaka, B. M., Krause, G., and Gershengorn, M. C. (2006) A low molecular weight agonist signals by binding to the transmembrane domain of thyroid-stimulating hormone receptor (TSHR) and luteinizing hormone/chorionic gonadotropin receptor (LHCGR). J. Biol. Chem. 281, 9841-9844
10. Neumann, S., Kleinau, G., Costanzi, S., Moore, S., Jiang, J. K., Raaka, B. M., Thomas, C. J., Krause, G., and Gershengorn, M. C. (2008) A low-molecular-weight antagonist for the human thyrotropin receptor with therapeutic potential for hyperthyroidism. Endocrinology 149, 5945-5950
11. Neumann, S., Huang, W., Titus, S., Krause, G., Kleinau, G., Alberobello, A. T., Zheng, W., Southall, N. T., Inglese, J., Austin, C. P., Celi, F. S., Gavrilova, O., Thomas, C. J., Raaka, B. M., and Gershengorn, M. C. (2009) Small-molecule agonists for the thyrotropin receptor stimulate thyroid function in human thyrocytes and mice. Proc. Natl. Acad. Sci. U. S. A. 106, 12471-12476
12. Surgand, J. S., Rodrigo, J., Kellenberger, E., and Rognan, D. (2006) A chemogenomic analysis of the transmembrane binding cavity of human G-protein-coupled receptors. Proteins 62, 509-538
13. Heitman, L. H., and Ijzerman, A. P. (2008) G protein-coupled receptors of the hypothalamic-pituitary-gonadal axis: a case for Gnrh, LH, FSH, and GPR54 receptor ligands. Med. Res. Rev. 28, 975-1011
14. Moore, S., Jaeschke, H., Kleinau, G., Neumann, S., Costanzi, S., Jiang, J. K., Childress, J., Raaka, B. M., Colson, A., Paschke, R., Krause, G., Thomas, C. J., and Gershengorn, M. C. (2006) Evaluation of small-molecule modulators of the luteinizing hormone/choriogonadotropin and thyroid stimulating hormone receptors: structure-activity relationships and selective binding patterns. J. Med. Chem. 49, 3888-3896
15. Parnot, C., Miserey-Lenkei, S., Bardin, S., Corvol, P., and Clauser, E. (2002) Lessons from constitutively active mutants of G protein-coupled receptors. Trends Endocrinol. Metab. 13, 336-343
16. Smith, B. J., Wales, M. R., and Perry, M. J. (1993) Assays of cyclic nucleotides. A review of current techniques. Appl. Biochem. Biotechnol. 41, 189-218
17. Hanson, M. A., and Stevens, R. C. (2009) Discovery of new GPCR biology: one receptor structure at a time. Structure 17, 8-14
18. Rosenbaum, D. M., Rasmussen, S. G., and Kobilka, B. K. (2009) The structure and function of G-protein-coupled receptors. Nature 459, 356-363
19. Kobilka, B., and Schertler, G. F. (2008) New G-protein-coupled receptor crystal structures: insights and limitations. Trends Pharmacol. Sci. 29, 79-83
20. Lodowski, D. T., Angel, T. E., and Palczewski, K. (2009) Comparative analysis of GPCR crystal structures. Photochem. Photobiol. 85, 425-430
21. Park, J. H., Scheerer, P., Hofmann, K. P., Choe, H. W., and Ernst, O. P. (2008) Crystal structure of the ligand-free Gprotein-coupled receptor opsin. Nature 454, 183-187
22. Laskowski, R. A., Moss, D. S., and Thornton, J. M. (1993) Main-chain bond lengths and bond angles in protein structures. J. Mol. Biol. 231, 1049-1067
23. Kleinau, G., Claus, M., Jaeschke, H., Mueller, S., Neumann, S., Paschke, R., and Krause, G. (2007) Contacts between extracellular loop two and transmembrane helix six determine basal activity of the thyroid-stimulating hormone receptor. J. Biol. Chem. 282, 518-525
24. sα mutations in toxic thyroid nodules in geographical regions with different iodine supply in Turkey. Eur. J. Endocrinol. 155, 535-545
25. Ballesteros, J. A., and Weinstein, H. (1995) Integrated methods for the construction of three-dimensional models and computational probing of structure-function relationships in G-protein coupled receptors. Methods Neurosci. 25, 366-428
26. Kleinau, G., Brehm, M., Wiedemann, U., Labudde, D., Leser, U., and Krause, G. (2007) Implications for molecular mechanisms of glycoprotein hormone receptors using a new sequence-structure-function analysis resource. Mol. Endocrinol. 21, 574-580
27. Deflorian, F., Engel, S., Colson, A. O., Raaka, B. M., Gershengorn, M. C., and Costanzi, S. (2008) Understanding the structural and functional differences between mouse thyrotropin-releasing hormone receptors 1 and 2. Proteins 71, 783-794
28. Kleinau, G., Jaeschke, H., Mueller, S., Worth, C. L., Paschke, R., and Krause, G. (2008) Molecular and structural effects of inverse agonistic mutations on signaling of the thyrotropin receptor - a basally active GPCR. Cell. Mol. Life Sci. 65, 3664-3676
29. Seifert, R., and Wenzel-Seifert, K. (2002) Constitutive activity of G-protein-coupled receptors: cause of disease and common property of wild-type receptors. Naunyn Schmiedebergs Arch. Pharmacol. 366, 381-416
30. Rodien, P., Ho, S. C., Vlaeminck, V., Vassart, G., and Costagliola, S. (2003) Activating mutations of TSH receptor. Ann. Endocrinol. (Paris) 64, 12-16
31. Sum, C. S., Tikhonova, I. G., Costanzi, S., and Gershengorn, M. C. (2009) Two arginine-glutamate ionic locks near the extracellular surface of FFAR1 gate receptor activation. J. Biol. Chem. 284, 3529-3536
32. Schwartz, T. W., Frimurer, T. M., Holst, B., Rosenkilde, M. M., and Elling, C. E. (2006) Molecular mechanism of 7TM receptor activation - a global toggle switch model. Annu. Rev. Pharmacol. Toxicol. 46, 481-519
33. Kleinau, G., Jaeschke, H., Mueller, S., Raaka, B. M., Neumann, S., Paschke, R., and Krause, G. (2008) Evidence for cooperative signal triggering at the extracellular loops of the TSH receptor. FASEB J. 22, 2798-2808
34. Kobilka, B. K., and Deupi, X. (2007) Conformational complexity of G-protein-coupled receptors. Trends Pharmacol. Sci. 28, 397-406
35. Holst, B., Holliday, N. D., Bach, A., Elling, C. E., Cox, H. M., and Schwartz, T. W. (2004) Common structural basis for constitutive activity of the ghrelin receptor family. J. Biol. Chem. 279, 53806-53817 (Pubitemid 40051890)
36. Konopka, J. B., Margarit, S. M., and Dube, P. (1996) Mutation of Pro-258 in transmembrane domain 6 constitutively activates the G protein-coupled α-factor receptor. Proc. Natl. Acad. Sci. U. S. A. 93, 6764-6769