Molecular dynamics simulations reveal multiple pathways of ligand dissociation from thyroid hormone receptors

Biophysical Journal

Volumn 89, Issue 3, 2005, Pages 2011-2023

  Martínez, Leandro ^a   Sonoda, Milton T ^a   Webb, Paul ^b   Baxter, John D ^b   Skaf, Munir S ^a   Polikarpov, Igor ^c  

^a UNIVERSITY OF CAMPINAS   (Brazil)

^b UNIVERSITY OF CALIFORNIA   (United States)

^c UNIVERSITY OF SÃO PAULO   (Brazil)

Author keywords

[No Author keywords available]

Indexed keywords

LIGAND; LIOTHYRONINE; PROTEIN; THYROID HORMONE RECEPTOR;

ARTICLE; COMPUTER SIMULATION; CONFORMATION; CRYSTAL STRUCTURE; LIGAND BINDING; MOLECULAR DYNAMICS; SIMULATION; X RAY ANALYSIS;

EID: 24144439756     PISSN: 00063495     EISSN: None     Source Type: Journal    
DOI: 10.1529/biophysj.105.063818     Document Type: Article

References (67)

1. Ribeiro, R. C. J., P. J. Kushner, and J. D. Baxter. 1995. The nuclear hormone receptor gene superfamily. Annu. Rev. Med. 46:443-453.
2. Bourguet, W., P. Germain, and H. Gronemeyer. 2000. Nuclear receptor ligand-binding domains: three-dimensional structures, molecular interactions and pharmacological implications. Trends Pharmacol. Sci. 21:381-388.
3. Gronemeyer, H., J. A. Gustafsson, and V. Laudet. 2004. Principles for modulation of the nuclear receptor superfamily. Nat. Rev. Drug Discov. 3:950-964.
4. Apriletti, J. W., R. C. J. Ribeiro, R. L. Wagner, W. Feng, P. Webb, P. J. Kushner, B. L. West, S. Nilsson, T. S. Scanlan, R. J. Fletterick, and J. D. Baxter. 1998. Molecular and structural biology of thyroid hormone receptors. Clin. Exp. Pharmacol. Physiol. Suppl. 25:S2-S11 (Suppl. S.).
5. Laudet, V., and H. Gronemeyer. 2002. The Nuclear Receptor Facts Book, 1st ed. Academic Press, London.
6. Wagner, R. L., J. W. Apriletti, M. E. McGrath, B. L. West, J. D. Baxter, and R. J. Fletterick. 1995. A structural role for hormone in the thyroid hormone receptor. Nature. 378:690-697.
7. Nettles, K. W., and G. L. Greene. 2005. Ligand control of coregulator recruitment to nuclear receptors. Annu. Rev. Physiol. 67:309-333.
8. Francis, G. A., E. Fayard, F. Picard, and J. Auwerx. 2003. Nuclear receptors and the control of metabolism. Annu. Rev. Physiol. 65:261-311.
9. Johnson, B. A., E. M. Wilson, Y. Li, D. E. Moller, R. G. Smith, and G, Zhou. 2000. Ligand-induced stabilization of PPARgamma monitored by NMR spectroscopy: implications for nuclear receptor activation. J. Mol. Biol. 298:187-194.
10. Pissios, P., I. Tzameli, P. Kushner, and D. D. Moore. 2000. Dynamic stabilization of nuclear receptor ligand binding domains by hormone or corepressor binding. Mol. Cell. 6:245-253.
11. Gee, A. C., and J. A. Katzenellenbogen. 2001. Probing conformational changes in the estrogen receptor: evidence for a partially unfolded intermediate facilitating ligand binding and release. Mol. Endocrinol. 15:421-128.
12. Kallenberger, B. C., J. D. Love, V. K. Chatterjee, and J. W. Schwabe. 2003. A dynamic mechanism of nuclear receptor activation and its perturbation in a human disease. Nat. Struct. Biol. 10:136-140.
13. Weatherman, R. V., R. J. Fletterick, and T. S. Scanlan. 1999. Nuclear-receptor ligands and ligand-binding domains. Annu. Rev. Biochem. 68:559-581.
14. Webb, P., N. H. Nguyen, G. Chiellini, H. A. Yoshihara, S. T. Cunha Lima, J. W. Apriletti, R. C. Ribeiro, A. Marimuthu, B. L. West, P. Goede, K. Mellstrom, S. Nilsson, and others. 2002. Design of thyroid hormone receptor antagonists from first principles. J. Steroid Biochem. Mol. Biol. 83:59-73.
15. Glass, C. K., and M. G. Rosenfeld. 2000. The coregulator exchange in transcriptional functions of nuclear receptors. Genes Dev. 14:121-141.
16. Renaud, J. P., N. Rochel, M. Ruff, V. Vivat, P. Chambon, H. Gronemeyer, and D. Moras. 1995. Crystal structure of the RAR-gamma ligand-binding domain bound to all-trans retinoic acid. Nature. 378:681-689.
17. Blondel, A., J. P. Renaud, S. Fischer, D. Moras, and M. Karplus. 1999. Retinoic acid receptor: a simulation analysis of retinoic acid binding and the resulting conformational changes. J. Mol. Biol. 291:101-115.
18. Egea, P. F., A. Mitschler, N. Rochel, M. Ruff, P. Chambon, and D. Moras. 2000. Crystal structure of the human RXRalpha ligand-binding domain bound to its natural ligand: 9-cis retinoic acid. EMBO J. 19:2592-2601.
19. Carlson, K. E., I. Choi, A. Gee, B. S. Katzenellenbogen, and J. A. Katzenellenbogen. 1997. Altered ligand binding properties and enhanced stability of a constitutively active estrogen receptor: evidence that an open pocket conformation is required for ligand interaction. Biochemistry. 36:14897-14905.
20. Gee, A. C., K. E. Carlson, P. G. Martini, B. S. Katzenellenbogen, and J. A. Katzenellenbogen. 1999. Coactivator peptides have a differential stabilizing effect on the binding of estrogens and antiestrogens with the estrogen receptor. Mol. Endocrinol. 13:1912-1923.
21. Darimont, B. D., R. L. Wagner, J. W. Apriletti, M. R. Stallcup , P. J. Kushner, J. D. Baxter, R. J. Fletterick, and K. R. Yamamoto. 1998. Structure and specificity of nuclear receptor-coactivator interactions. Genes Dev. 12:3343-3356.
22. Wagner, R. L., B. R. Huber, A. K. Shiau, A. Kelly, S. T. Cunha Lima, T. S. Scanlan, J. W. Apriletti, J. D. Baxter, B. L. West, and R. J. Fletterick. 2001. Hormone selectivity in thyroid hormone receptors. Mol. Endocrinol. 15:398-410.
23. Sandler, B., P. Webb, J. W. Apriletti, B. R. Huber, M. Togashi, S. T. Cunha Lima, S. Juric, S. Nilsson, R. Wagner, R. J. Fletterick, and J. D. Baxter. 2004. Thyroxine-thyroid hormone receptor interactions. J. Biol. Chem. 279:55801-55808.
24. Huber, B. R., M. Descloreaux, B. L. West, S. T. Cunha Lima, H. T. Nguyen, J. D. Baxter, A. Ingraham, and R. J. Fletterick. 2003. Thyroid hormone receptor-beta mutations conferring hormone resistance and reduced corepressor release exhibit decreased stability in the N-terminal ligand-binding domain. Mol. Endocrinol. 17:107-116.
25. Huber, B. R., B. Sandler, B. L. West, S. T. Cunha Lima, H. T. Nguyen, J. W. Apriletti, J. D. Baxter, and R. J. Fletterick. 2003. Two RTH mutants with impaired hormone binding. Mol. Endocrinol. 17:643-652.
26. Nolte, R. T., G. B. Wisely, S. Westin, J. E. Cobb, M. H. Lambert, R. Kurokawa, M. G. Rosenfeld, T. M. Willson, C. K. Glass, and M. V. Milburn. 1998. Ligand binding and co-activator assembly of the peroxisome proliferator- activated receptor gamma. Nature. 395:137-143.
27. Borngraeber, S., M. J. Budny, G. Chiellini, S. T. Cunha-Lima, M. Togashi, P. Webb, J. D. Baxter, T. S. Scanlan, and R. J. Fletterick. 2003. Ligand selectivity by seeking hydrophobicity in thyroid hormone receptor. Proc. Natl. Acad. Sci. USA. 100:15358-15363.
28. Elber, R., and M. Karplus. 1990. Enhanced sampling in molecular dynamics: use of time-dependent Hartree approximation for a simulation of carbon monoxide diffusion through myoglobin. J. Am. Chem. Soc. 112:9161-9175.
29. Quillin, M. L., T. S. Li, J. S. Olson, G. N. Phillips, Y. Dou, M. Ikedasaito, R. Regan, M. Carlson, Q. H. Gibson, H. Y. Li, and R. Elber. 1995. Structural and functional effects of apolar mutations of the distal valine in myoglobin. J. Mol. Biol. 245:416-436.
30. Jensen, M. O., S. Park, E. Tajkhorshid, and K. Schulten. 2002. Energetics of glycerol conduction through aquaglyceroporin GlpF. Proc. Natl. Acad. Sci. USA. 99:6731-6736.
31. Kosztin, D., S. Izrailev, and K. Schulten. 1999. Unbinding of retinoic acid from its receptor studied by steered molecular dynamics. Biophys. J. 76:188-197.
32. Budhu, A. S., and N. Noy. 2000. On the role of the carboxyl-terminal helix of RXR in the interactions of the receptor with ligand. Biochemistry. 39:4090-4095.
33. Baxter, J. D., P. Goede, J. W. Apriletti, B. L. West, W. Feng, K. Mellstrom, R. J. Fletterick, R. L. Wagner, P. J. Kushner, R. C. Ribeiro, P. Webb, T. S. Scanlan, and S. Nilsson. 2002. Structure-based design and synthesis of a thyroid hormone receptor (TR) antagonist. Endocrinology. 143:517-524.
34. Ye, L., Y. L. Li, K. Mellstrom, C. Mellin, L. G. Bladh, K. Koehler, N. Garg, A. M. Garcia Collazo, C. Litten, B. Husman, K. Persson, J. Ljunggren, and others. 2003. Thyroid receptor ligands. 1. Agonist ligands selective for the thyroid receptor beta1. J. Med. Chem. 46:1580-1588.
35. Ye, H. F., K. E. O'Reilly, and J. T. Koh. 2001. A subtype-selective thyromimetic designed to bind a mutant thyroid hormone receptor implicated in resistance to thyroid hormone. J. Am. Chem. Soc. 123:1521-1522.
36. Baxter, J. D., W. H. Dillmann, B. L. West, R. Huber, J. D. Furlow, R. J. Fletterick, P. Webb, J. W. Apriletti, and T. S. Scanlan. 2001. Selective modulation of thyroid hormone receptor action. J. Steroid Biochem. Mol. Biol. 76:31-42.
37. Grover, G. J., D. M. Egan, P. G. Sleph, B. C. Beehler, G. Chiellini, N. H. Nguyen, J. D. Baxter, and T. S. Scanlan. 2004. Effects of the thyroid hormone receptor agonist GC-1 on metabolic rate and cholesterol in rats and primates: selective actions relative to 3,5,3′-triiodo-L-thyronine. Endocrinology. 145:1656-1661.
38. Baxter, J. D., P. Webb, G. Grover, and T. S. Scanlan. 2004. Selective activation of thyroid hormone signaling pathways by GC-1: a new approach to controlling cholesterol and body weight. Trends Endocrinol Metab. 15:154-157.
39. Grover, G. J., K. Mellstrom, L. Ye, J. Malm, Y. L. Li, L. G. Bladh, P. G. Sleph, M. A. Smith, R. George, B. Vennstrom, K. Mookhtiar, R. Horvath, and others. 2003. Selective thyroid hormone receptor-beta activation: a strategy for reduction of weight, cholesterol, and lipoprotein (a) with reduced cardiovascular liability. Proc. Natl. Acad. Sci. USA. 100:10067-10072.
40. Webb, P. 2004. Selective activators of thyroid hormone receptors. Expert Opin. Investig. Drugs. 13:489-500.
41. Nguyen, N. H., J. W. Apriletti, S. T. Cunha Lima, P. Webb, J. D. Baxter, and T. S. Scanlan. 2002. Rational design and synthesis of a novel thyroid hormone antagonist that blocks coactivator recruitment. J. Med. Chem. 45:3310-3320.
42. Liu, D. C., and J. Nocedal. 1989. On the limited memory BFGS method for large-scale optimization. Math. Program. 45:503-528.
43. Ponder, J. W. 2001. TINKER Software Tools for Molecular Design. Version 3. 9.
44. Kraulis, P. J. 1991. Molscript-a program to produce both detailed and schematic plots of protein structures. J. Appl. Cryst. 24:946-950, Part 5.
45. Merrit, E. A., and D. J. Bacon. 1997. Raster3D: photorealistic molecular graphics. Methods Enzymol. 277:505-524.
46. Humphrey, W., A. Dalke, and K. Schulten. 1996. VMD: visual molecular dynamics. J. Mol. Graph. 14:33-38.
47. Verlet, L. 1967. Computer simulations on classical fluids. I. Thermodynamics properties of Lennard Jones Molecules. Phys. Rev. 159:98-103.
48. Gibson, Q. H., R. Regan, R. Elber, J. S. Olson, and T. E. Carver. 1992. Distal pocket residues affect picosecond ligand recombination in myoglobin-an experimental and molecular dynamics study of position 29 mutants. J. Biol. Chem. 267:22022-22034.
49. Scott, E. E., Q. H. Gibson, and J. S. Olson. 2001. Mapping the pathways for O2 entry into and exit from myoglobin. J. Biol. Chem. 267:5177-5188.
50. Brunori, M., and Q. H. Gibson. 2001. Cavities and packing defects in the structural dynamics of myoglobin. EMBO Rep. 2:674-679.
51. Ulitsky, A., and R. Elber. 1993. The thermal equilibrium aspects of the time dependent Hartree and the locally enhanced sampling approximations: formal properties, a correction, and computational examples for rare gas clusters. J. Chem. Phys. 98:3380-3388.
52. Straub, J. E., and M. E. Karplus. 1991. Energy equilibrium in the classical time-dependent Hartree approximation. J. Chem. Phys. 94:6737-6739.
53. Ulitsky, A., and R. Elber. 1994. Application of the locally enhanced sampling (LES) and a mean-field with binary collision correction (cLES) to the simulation of Ar diffusion and NO recombination in myoglobin. J. Phys. Chem. 98:1034-1043.
54. Kaminski, G. A., R. A. Friesner, J. Tirado-Rives, and W. L. Jorgensen. 2001. Evaluation and reparametrization of the OPLS-AA force field for proteins via comparison with accurate quantum chemical calculations on peptides. J. Phys. Chem. B. 105:6474-6487.
55. Sonoda, M. T., N. H. Moreira, L. Martinez, F. W. Fávero, S. M. Vechi. L. R. Martins, M.S. Skaf. 2004. A review on the dynamics of water. Braz. J. Phys. 34:3-16.
56. Martinez, L. 2003. Computational study fo thyroid hormone dissociation from its nuclear receptor. Master thesis. State University of Campinas, Campinas, SP, Brazil.
57. Jorgensen, W. L., D. S. Maxwell, and J. Tirado-Rives. 1996. Development and testing of the OPLS all-atom force field on conformational energetics and properties of organic liquids. J. Am. Chem. Soc. 118:11225-11236.
58. Blaney, J. M., P. K. Weiner, A. Dearing, P. A. Kollman, E. C. Jorgensen, S. J. Oatley, J. M. Burridge, and C. C. F. Blake. 1982. Molecular mechanics simulation of protein ligand interactions-binding of thyroid-hormone analogs to pre-albumin. J. Med. Chem. Soc. 104:6424-6434.
59. Frisch, M. J., et al. 2004. Gaussian, Inc., Wallingford CT.
60. Fetrow, J. S. 1995. Omega loops: nonregular secondary structures significant in protein function and stability. FASEB J. 9:708-717.
61. Brzozowski, A. M., A. C. Pike, Z. Dauter, R. E. Hubbard, T. Bonn, O. Engstrom, L. Ohman, G. L. Greene, J. A. Gustafsson, and M. Carlquist. 1997. Molecular basis of agonism and antagonism in the oestrogen receptor. Nature. 389:753-758.
62. Shiau, A. K., D. Barstad, P. M. Loria, L. Cheng, P. J. Kushner, D. A. Agard, and G. L. Greene. 1998. The structural basis of estrogen receptor/coactivator recognition and the antagonism of this interaction by tamoxifen. Cell. 95:927-937.
63. Kauppi, B., C. Jakob, M. Farnegardh, J. Yang, H. Ahola, M. Alarcon, K. Calles, O. Engstrom, J. Harlan, S. Muchmore, A. K. Ramqvist, and S. Thorell, and others. 2003. The three-dimensional structures of antagonistic and agonistic forms of the glucocorticoid receptor ligand-binding domain: RU-486 induces a transconformation that leads to active antagonism. J. Biol. Chem. 278:22748-22754.
64. Bledsoe, R. K., V. G. Montana, T. B. Stanley, C. J. Delves, C. J. Apolito, D. D. McKee, T. G. Consler, D. J. Parks, E. L. Stewart, T. M. Willson, M. H. Lambert, J. T. Moore, and others. 2002. Crystal structure of the glucocorticoid receptor ligand binding domain reveals a novel mode of receptor dimerization and coactivator recognition. Cell. 110:93-105.
65. Downes, M., M. A. Verdecia, A. J. Roecker, R. Hughes, J. B. Hogenesch, H. R. Kast-Woelbern, M. E. Bowman, J. L. Ferrer, A. M. Anisfeld, P. A. Edwards, J. M. Rosenfeld, J. G. Alvarez, and others. 2003. A chemical, genetic, and structural analysis of the nuclear bile acid receptor FXR. Mol. Cell. 11:1079-1092.
66. Sack, J. S., K. F. Kish, C. Wang, R. M. Attar, S. E. Kiefer, Y. An, G. Y. Wu, J. E. Scheffler, M. E. Salvati, S. R. Krystek Jr, R. Weinmann, and H. M. Einspahr. 2001. Crystallographic structures of the ligand-binding domains of the androgen receptor and its T877A mutant complexed with the natural agonist dihydrotestosterone. Proc. Natl. Acad. Sci. USA. 98:4904-4909.
67. Watkins, R. E., J. M. Maglich, L. B. Moore, G. B. Wisely, S. M. Noble, P. R. Davis-Searles, M. H. Lambert, S. A. Kliewer, and M. R. Redinbo. 2003. 2.1 A crystal structure of human PXR in complex with the St. John's wort compound hyperforin. Biochemistry. 42:1430-1438.