The antibodies against the computationally designed mimic of the glycoprotein hormone receptor transmembrane domain provide insights into receptor activation and suppress the constitutively activated receptor mutants

Journal of Biological Chemistry

Volumn 287, Issue 41, 2012, Pages 34514-34532

  Majumdar, Ritankar ^a   Railkar, Reema ^a   Dighe, Rajan R ^a  

^a INDIAN INSTITUTE OF SCIENCE   (India)

Author keywords

[No Author keywords available]

Indexed keywords

BASAL ACTIVITIES; CHIMERIC RECEPTORS; COMPUTATIONAL ANALYSIS; COMPUTATIONAL APPROACH; GLYCOPROTEIN HORMONE RECEPTORS; HORMONE BINDING; HORMONE RECEPTORS; HORMONE-RECEPTOR COMPLEX; INTER-DOMAIN; RECEPTOR ACTIVATION; RECEPTOR MUTANTS; TRANS-MEMBRANE DOMAINS; TRANSMEMBRANE DOMAIN; TRANSMEMBRANE HELICES;

ACTIVATION ANALYSIS; COMPUTATIONAL METHODS; ENDOCRINOLOGY; GLYCOPROTEINS; HORMONES; LIGANDS;

ANTIBODIES;

ANTIBODY; CYCLIC AMP; FOLLITROPIN RECEPTOR; LUTEINIZING HORMONE RECEPTOR; THYROTROPIN RECEPTOR;

ARTICLE; COMPLEX FORMATION; CONFORMATIONAL TRANSITION; CONTROLLED STUDY; GAIN OF FUNCTION MUTATION; GENE DELETION; HINGE REGION; HORMONE BINDING; MATHEMATICAL COMPUTING; MOLECULAR MODEL; POINT MUTATION; PRIORITY JOURNAL; PROTEIN DOMAIN; TRANSMEMBRANE DOMAIN;

ANTIBODIES, MONOCLONAL; HEK293 CELLS; HUMANS; MODELS, MOLECULAR; PROTEIN STRUCTURE, SECONDARY; PROTEIN STRUCTURE, TERTIARY; RECEPTORS, LH;

EID: 84867242964     PISSN: 00219258     EISSN: 1083351X     Source Type: Journal    
DOI: 10.1074/jbc.M112.355032     Document Type: Article

References (52)

1. Kristiansen, K. (2004) Molecular mechanisms of ligand binding, signaling, and regulation within the superfamily of G-protein-coupled receptors. Molecular modeling and mutagenesis approaches to receptor structure and function. Pharmacol. Ther. 103, 21-80
2. Fan, Q. R., and Hendrickson, W. A. (2005) Structure of human folliclestimulating hormone in complex with its receptor. Nature 433, 269-277
3. Moyle, W. R., Campbell, R. K., Rao, S. N., Ayad, N. G., Bernard, M. P., Han, Y., and Wang, Y. (1995) Model of human chorionic gonadotropin and lutropin receptor interaction that explains signal transduction of the glycoprotein hormones. J. Biol. Chem. 270, 20020-20031
4. Moyle, W. R., Xing, Y., Lin, W., Cao, D., Myers, R. V., Kerrigan, J. E., and Bernard, M. P. (2004) Model of glycoprotein hormone receptor ligand binding and signaling. J. Biol. Chem. 279, 44442-44459 (Pubitemid 39430850)
5. Moyle, W. R., Lin, W., Myers, R. V., Cao, D., Kerrigan, J. E., and Bernard, M. P. (2005) Models of glycoprotein hormone receptor interaction. Endocrine 26, 189-205 (Pubitemid 41271084)
6. Mueller, S., Jaeschke, H., Günther, R., and Paschke, R. (2010) The hinge region: an important receptor component for GPHR function. Trends Endocrinol. Metab. 21, 111-122
7. Agrawal, G., and Dighe, R. R. (2009) Critical involvement of the hinge region of the follicle-stimulating hormone receptor in the activation of the receptor. J. Biol. Chem. 284, 2636-2647
8. Neumann, S., Claus, M., and 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 (Pubitemid 40575809)
9. 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
10. Hicks, D., and Barnstable, C. J. (1987) Different rhodopsin monoclonal antibodies reveal different binding patterns on developing and adult rat retina. J. Histochem. Cytochem 35, 1317-1328
11. Blanpain, C., Vanderwinden, J. M., Cihak, J., Wittamer, V., Le Poul, E., Issafras, H., Stangassinger, M., Vassart, G., Marullo, S., and Schlndorff, D. (2002) Multiple active states and oligomerization of CCR5 revealed by functional properties of monoclonal antibodies. Mol. Biol. Cell 13, 723-737 (Pubitemid 34165096)
12. Eswar, N., Webb, B., Marti-Renom, M. A., Madhusudhan, M., Eramian, D., Shen, M. Y., Pieper, U., and Sali, A. (2007) Comparative protein structure modeling using MODELLER. Curr. Protoc. Protein Sci., Chapter 2, Unit 2.9
13. Worth, C. L., Kleinau, G., and Krause, G. (2009) Comparative sequence and structural analyses of G-protein-coupled receptor crystal structures and implications for molecular models. PLoS ONE 4, e7011
14. Hildebrand, P. W., Goede, A., Bauer, R. A., Gruening, B., Ismer, J., Michalsky, E., and Preissner, R. (2009) SuperLooper. A prediction server for the modeling of loops in globular and membrane proteins. Nucleic Acids Res. 37, W571-W574
15. Canutescu, A. A., and Dunbrack, R. L., Jr. (2003) Cyclic coordinate descent. A robotics algorithm for protein loop closure. Protein Sci. 12, 963-972 (Pubitemid 36505431)
16. Spassov, V. Z., Flook, P. K., and Yan, L. (2008) LOOPER. A molecular mechanics-based algorithm for protein loop prediction. Protein Eng. Des. Sel. 21, 91-100 (Pubitemid 351301921)
17. Lee, B., Sharron, M., Blanpain, C., Doranz, B. J., Vakili, J., Setoh, P., Berg, E., Liu, G., Guy, H. R., Durell, S. R., Parmentier, M., Chang, C. N., Price, K., Tsang, M., and Doms, R. W. (1999) Epitope mapping of CCR5 reveals multiple conformational states and distinct but overlapping structures involved in chemokine and coreceptor function. J. Biol. Chem. 274, 9617-9626
18. Yeagle, P. L., Alderfer, J. L., and Albert, A. D. (1997) Three-dimensional structure of the cytoplasmic face of the G protein receptor rhodopsin. Biochemistry 36, 9649-9654 (Pubitemid 27364675)
19. 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
20. Brooks, B. R., Brooks, C. L., 3rd, Mackerell, A. D., Jr., Nilsson, L., Petrella, R. J., Roux, B., Won, Y., Archontis, G., Bartels, C., Boresch, S., Caflisch, A., Caves, L., Cui, Q., Dinner, A. R., Feig, M., Fischer, S., Gao, J., Hodoscek, M., Im, W., Kuczera, K., Lazaridis, T., Ma, J., Ovchinnikov, V., Paci, E., Pastor, R. W., Post, C. B., Pu, J. Z., Schaefer, M., Tidor, B., Venable, R. M., Woodcock, H. L., Wu, X., Yang, W., York, D. M., and Karplus, M. (2009) CHARMM. The biomolecular simulation program. J. Comput. Chem. 30, 1545-1614
21. Roy, A., Kucukural, A., and Zhang, Y. (2010) I-TASSER. A unified platform for automated protein structure and function prediction. Nat. Protoc. 5, 725-738
22. Heinig, M., and Frishman, D. (2004) STRIDE. A web server for secondary structure assignment from known atomic coordinates of proteins. Nucleic Acids Res. 32, W500-W502 (Pubitemid 38997383)
23. Rydzanicz, R., Zhao, X. S., and Johnson, P. E. (2005) Assembly PCR oligo maker. A tool for designing oligodeoxynucleotides for constructing long DNA molecules for RNA production. Nucleic Acids Res. 33, W521-W525 (Pubitemid 44529975)
24. Majumdar, R., and Dighe, R. R. (2012) The hinge region of human thyroidstimulating hormone (TSH) receptor operates as a tunable switch between hormone binding and receptor activation. PLoS ONE 7, e40291
25. Majumdar, R., Railkar, R., and Dighe, R. R. (2012) Insights into differential modulation of receptor function by hinge region using novel agonistic lutropin receptor and inverse agonistic thyrotropin receptor antibodies. FEBS Lett. 586, 810-817
26. Wang, W., and Malcolm, B. A. (2002) Two-stage polymerase chain reaction protocol allowing introduction of multiple mutations, deletions, and insertions using QuikChange site-directed mutagenesis. Methods Mol. Biol. 182, 37-43
27. Dighe, R. R., and Moudgal, N. R. (1983) Use of α- and β-subunit specific antibodies in studying interaction of hCG with Leydig cell receptors. Arch. Biochem. Biophys. 225, 490-499 (Pubitemid 13010240)
28. Saha, S., Majumdar, R., Dighe, R. R., and Chakravarty, A. R. (2010) Enhanced photodynamic effect of cobalt(III) dipyridophenazine complex on thyrotropin receptor expressing HEK293 cells. Metallomics 2, 754-765
29. Neumann, S., Krause, G., Chey, S., and Paschke, R. (2001) A free carboxylate oxygen in the side chain of position 674 in transmembrane domain 7 is necessary for TSH receptor activation. Mol. Endocrinol. 15, 1294-1305 (Pubitemid 32703478)
30. Claus, M., Jaeschke, H., Kleinau, G., Neumann, S., Krause, G., and Paschke, R. (2005) A hydrophobic cluster in the center of the third extracellular loop is important for thyrotropin receptor signaling. Endocrinology 146, 5197-5203 (Pubitemid 41653033)
31. Bulheller, B. M., and Hirst, J. D. (2009) DichroCalc. Circular and linear dichroism online. Bioinformatics 25, 539-540
32. 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 (Pubitemid 47076654)
33. Zeng, H., Phang, T., Song, Y. S., Ji, I., and Ji, T. H. (2001) The role of the hinge region of the luteinizing hormone receptor in hormone interaction and signal generation. J. Biol. Chem. 276, 3451-3458
34. Nishi, S., Nakabayashi, K., Kobilka, B., and Hsueh, A. J. (2002) The ectodomain of the luteinizing hormone receptor interacts with exoloop 2 to constrain the transmembrane region. Studies using chimeric human and fly receptors. J. Biol. Chem. 277, 3958-3964 (Pubitemid 34968649)
35. Zhang, M., Tong, K. P., Fremont, V., Chen, J., Narayan, P., Puett, D., Weintraub, B. D., and Szkudlinski, M. W. (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 (Pubitemid 32269043)
36. Nurwakagari, P., Breit, A., Hess, C., Salman-Livny, H., Ben-Menahem, D., and Gudermann, T. (2007) A conformational contribution of the luteinizing hormone-receptor ectodomain to receptor activation. J. Mol. Endocrinol. 38, 259-275 (Pubitemid 46351608)
37. Ho, S. C., Van Sande, J., Lefort, A., Vassart, G., and 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 (Pubitemid 32575510)
38. Wonerow, P., Neumann, S., Gudermann, T., and Paschke, R. (2001) Thyrotropin receptor mutations as a tool to understand thyrotropin receptor action. J. Mol. Med. 79, 707-721 (Pubitemid 34025119)
39. Heymann, B., and Grubmüller, H. (2001) Molecular dynamics force probe simulations of antibody/antigen unbinding. entropic control and nonadditivity of unbinding forces. Biophys. J. 81, 1295-1313 (Pubitemid 32783574)
40. Gadkari, R. A., Sandhya, S., Sowdhamini, R., and Dighe, R. R. (2007) The antigen binding sites of various hCG monoclonal antibodies show homology to different domains ofLHreceptor. Mol. Cell. Endocrinol. 260, 23-32 (Pubitemid 44792353)
41. Yoo, J., Zeng, H., Ji, I., Murdoch, W. J., and Ji, T. H. (1993) COOH-terminal amino acids of the α subunit play common and different roles in human choriogonadotropin and follitropin. J. Biol. Chem. 268, 13034-13042 (Pubitemid 23307715)
42. Shinozaki, H., Fanelli, F., Liu, X., Jaquette, J., Nakamura, K., and Segaloff, D. L. (2001) Pleiotropic effects of substitutions of a highly conserved leucine in transmembrane helix III of the human lutropin/ choriogonadotropin receptor with respect to constitutive activation and hormone responsiveness. Mol. Endocrinol. 15, 972-984 (Pubitemid 32510643)
43. Kaneshige, M., Haraguchi, K., Endo, T., Anzai, E., and Onaya, T. (1995) The functional significance of the second extracellular loop of thyrotropin receptor in thyrotropin- and thyroid stimulating antibody-dependent signal transduction. Horm. Metabol. Res. 27, 267-271
44. Dupakuntla, M., and Mahale, S. D. (2010) Accessibility of the extracellular loops of follicle stimulating hormone receptor and their role in hormone-receptor interaction. Mol. Cell. Endocrinol. 315, 131-137
45. Gustavsson, B., Westermark, B., and Heldin, N. E. (1994) Point mutations of the thyrotropin receptor determining structural requirements for its ability to bind thyrotropin and to stimulate adenylate cyclase activity. Biochem. Biophys. Res. Commun. 199, 612-618 (Pubitemid 24181705)
46. Kosugi, S., Matsuda, A., Hai, N., Aoki, N., Sugawa, H., and Mori, T. (1997) Aspartate-474 in the first exoplasmic loop of the thyrotropin receptor is crucial for receptor activation. FEBS Lett. 406, 139-141 (Pubitemid 27156976)
47. 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 (Pubitemid 34654459)
48. Van Sande, J., Massart, C., Costagliola, S., Allgeier, A., Cetani, F., Vassart, G., and Dumont, J. E. (1996) Specific activation of the thyrotropin receptor by trypsin. Mol. Cell. Endocrinol. 119, 161-168 (Pubitemid 26188738)
49. Vlaeminck-Guillem, V., Ho, S. C., Rodien, P., Vassart, G., and 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 (Pubitemid 34297743)
50. Mizutori, Y., Chen, C. R., McLachlan, S. M., and Rapoport, B. (2008) The thyrotropin receptor hinge region is not simply a scaffold for the leucinerich domain but contributes to ligand binding and signal transduction. Mol. Endocrinol. 22, 1171-1182 (Pubitemid 351629617)
51. Kleinau, G., Jäschke, H., Neumann, S., Lättig, J., Paschke, R., and Krause, G. (2004) Identification of a novel epitope in the thyroid-stimulating hormone receptor ectodomain acting as intramolecular signaling interface. J. Biol. Chem. 279, 51590-51600 (Pubitemid 40017910)
52. Jaeschke, H., Neumann, S., Kleinau, G., Mueller, S., Claus, M., Krause, G., and Paschke, R. (2006) An aromatic environment in the vicinity of serine 281 is a structural requirement for thyrotropin receptor function. Endocrinology 147, 1753-1760