Selected Publications

Yumoto F, Nguyen P, Sablin EP, Baxter JD, Webb P, Fletterick RJ. (2011) Structural Basis of Coactivation of Nuclear Receptor LRH-1 by beta-catenin. Proc Natl Acad Sci USA.109(1): 143-8.

De Leon JT, Iwai A, Feau C, Garcia Y, Balsiger HA, Storer CL, Suro RM, Garza KM, Lee S, Kim YS, Chen Y, Ning YM, Riggs DL, Fletterick RJ, Guy RK, Trepel JB, Neckers LM, Cox MB. (2011) Targeting the regulation of androgen receptor signaling by the heat shock protein 90 cochaperone FKBP52 in prostate cancer cells. Proc Natl Acad Sci U S A. 108(29): 11878-83.

Buzón V, Carbó LR, Estruch SB, Fletterick RJ, Estébanez-Perpiñá E. (2011) A conserved surface on the ligand binding domain of nuclear receptors for allosteric control. Mol Cell Endocrinol. 348(2): 394-402.

Benod C, Vinogradova MV, Jouravel N, Kim GE, Fletterick RJ, Sablin EP (2011) Nuclear receptor liver receptor homologue 1 (LRH-1) regulates pancreatic cancer cell growth and proliferation. Proc. Natl. Acad. Sci. USA 108(41): 16927-16931.

Hjelm R, Bennett Stone D, Fletterick RJ, and RA Mendelson. (2010) Decoration of microtubules in solution by the kinesin-14, Ncd. Acta Cryst. D66, 1218–1223

Wilbur JD, Hwang PK, Ybe JA, Lane M, Sellers BD, Jacobson MP, Fletterick RJ, Brodsky FM. (2010) Conformation switching of clathrin light chain regulates clathrin lattice assembly. Dev Cell. 18(5): 841-8.

Pfaff SJ and Fletterick RJ. (2010) Hormone binding and co-regulator binding to the glucocorticoid receptor are allosterically coupled. J Biol Chem 285(20): 15256-67.

Wilbur JD, Hwang PK, Brodsky FM, Fletterick RJ. (2010) Accommodation of structural rearrangements in the huntingtin-interaction protein 1 coiled-coil domain. Acta. Crystallogr. D. Biol Crystallogr. 66(Pt 3):314-8.

Vinogradova MV, Malanina GG, Reddy AS, Fletterick RJ. (2009)  Structure of the complex of a mitotic kinesin with its calcium binding regulator.  Proc Natl Acad Sci U S A. 106(20): 8175-9.

Sablin EP, Blind RD, Krylova IN, Ingraham JG, Cai F, Williams JD, Fletterick RJ and HA Ingraham (2009) Structure of SF-1 bound by different phospholipids: Evidence for regulatory ligands. Mol Endocrinol. 23(1): 25-34.

Sablin EP, Woods A, Krylova IN, Ingraham HA and RJ Fletterick. (2008) The Structure of corepressor DAX-1 bound to its target nuclear receptor LRH-1. Proc. Natl.Acad. Sci. 2105(47): 18390-5.

Cruz LA, Estébanez-Perpiñá E, Pfaff S, Borngraeber S, Bao N, Blethrow J, Fletterick RJ, England PM. (2008)  6-Azido-7-nitro-1,4-dihydroquinoxaline-2,3-dione (ANQX) forms an irreversible bond to the active site of the GluR2 AMPA Receptor. J Med Chem. 51(18): 5856-60.

Wilbur JD, Chen CY, Manalo V, Hwang PK, Fletterick RJ, Brodsky FM. (2008) Actin binding by Hip1 (huntingtin-interacting protein 1) and Hip1R (Hip1-related protein) is regulated by clathrin light chain. J Biol Chem. 283(47): 32870-9.

Jouravel N, Sablin E, Fletterick RJ.  (2008)  Molecular basis for dimer formation of TRb variant D355R. PROTEINS:  Structure, Function & Bioinformatics 75(1): 111-117.

Vinogradova M, Malanina G, Reddy V, Reddy A and RJ Fletterick. (2008)  Structural dynamics of the microtubule binding and regulatory elements in the kinesin-like calmodulin binding protein. J Structural Biology 163(1): 76-83.

Jouravel N, Sablin E, Arnold LA, Guy RK and RJ Fletterick. (2007) Interaction between the androgen receptor and a segment of its corepressor SHP. Acta Cryst. D63, 1198–1200

Arnold LA, Kosinski A, Estébanez-Perpiñá E., Fletterick RJ, and RK Guy. (2007) Inhibitors of the interaction of a thyroid hormone receptor and coactivators: Preliminary structure-activity relationships. J Medicinal Chemistry 50(22): 5269-80.

Estébanez-Perpiñá, E., Jouravel, N.and Fletterick, R.J. Developing therapeutic agents for androgen-independent prostate cancer.  Expert Opinion on Drug Discovery, Volume 2, Number 10, October 2007, pp. 1341-1355(15)  Publisher: Informa Healthcare

Estébanez-Perpiñá, E., Jouravel, N., Arnold, L.A., Togashi, M., Mar, E., Sablin, E., Nguyen, P., R. Baxter, J.D., Webb, P., Guy, R. K. and Fletterick, R.J. (2007) Structural insight into the mode of action of a direct inhibitor of coregulator binding to the thyroid hormone receptor.  Molecular Endocrinology (12): 2919-28.

Estébanez-Perpiñá, E., Arnold A, Nguyen P, Rodriguez E, Mar E, Bateman R, Pallai P, Shokat KM, Baxter JD, Guy RK, Webb P and RJ Fletterick.  (2007) A surface on the androgen receptor that allosterically regulates coactivator binding. Proc Natl Acad Sci U S A (PNAS) 104(41):16074-9.

Wang SX, Pandey KC, Scharfstein J, Whisstock J, Huang RK, Jacobelli J, Fletterick RJ, Rosenthal PJ, Abrahamson M, Brinen LS, Rossi A, Sali A, McKerrow JH. (2007) The structure of chagasin in complex with a cysteine protease clarifies the binding mode and evolution of an inhibitor family. Structure 15(5): 535-43.

Vinogradova MV, Stone DB, Malanina GG, Mendelson RA and RJ Fletterick. (2007) Ca Ion and the Troponin Switch. In: Regulatory Mechanisms of Striated Muscle Contraction. Ed. Ebashi and Ohtsuki, Springer.  Proceedings of symposium entitled “Regulatory Proteins of Striated Muscle – Structure, Function and Disorder (33rd NIPS Conference), Okazaki, Japan, 2005.  Volume 592, pp. 47-57.

Luginbuhl B, Kanyo Z, Jones RM, Fletterick RJ, Prusiner SB, Cohen FE, Williamson RA, Burton DR, Pluckthun A. (2006) Directed evolution of an anti-prion protein scFv fragment to an affinity of 1 pM and its structural interpretation. J Mol Biol. 363(1): 75-97.

Wang SX, Pandey KC, Somoza JR, Sijwali PS, Kortemme T, Brinen LS, Fletterick RJ, Rosenthal PJ, McKerrow JH. (2006) Structural basis for unique mechanisms of folding and hemoglobin binding by a malarial protease. Proc Natl Acad Sci U S A. 103(31): 11503-8.

Arnold LA, Estebanez-Perpina E, Togashi M, Shelat A, Ocasio CA, McReynolds AC, Nguyen P, Baxter JD, Fletterick RJ, Webb P, Guy RK. (2006) A high-throughput screening method to identify small molecule inhibitors of thyroid hormone receptor coactivator binding. Sci STKE (341):pl3.

Pirani A, Vinogradova MV, Curmi PM, King WA, Fletterick RJ, Craig R, Tobacman LS, Xu C, Hatch V, Lehman W. (2006) An atomic model of the thin filament in the relaxed and ca(2+)-activated States.  J Mol Biol. 357(3): 707-17.

Blumenschein TM, Stone DB, Fletterick RJ, Mendelson RA, Sykes BD. (2006) Dynamics of the C-Terminal Region of TnI in the Troponin Complex in Solution. Biophys J. 90(7): 2436-44.

Fletterick RJ. (2005) Molecular modelling of the androgen receptor axis: rational basis for androgen receptor intervention in androgen-independent prostate cancer.  BJU Int. Dec; 96 Suppl 2:2-9.

Arnold LA, Estebanez-Perpina E, Togashi M, Jouravel N, Shelat A, McReynolds AC, Mar E, Nguyen P, Baxter JD, Fletterick RJ, Webb P, Guy RK. (2005)  Discovery of small molecule inhibitors of the interaction of thyroid hormone receptor with transcriptional coregulators. J Biol Chem. 280(52):43048-55.

Blumenschein TM, Stone DB, Fletterick RJ, Mendelson RA, Sykes BD. (2005) alcium-dependent changes in the flexibility of the regulatory domain of TnC in the troponin complex. JBC. 280(23): 21924-32.

Togashi M, Borngraeber S, Sandler B, Fletterick RJ, Webb P and Baxter JD (2005) Conformational adaptations of nuclear receptor ligand binding domains to agonists: Potential for novel approaches to ligand design J. Steroid Biochem. Mol. Biol Proceedings of the 16th International Symposium of The Journal of Steroid Biochemistry and Molecular Biology 93,
Issues 2-5: 127-137.

Togashi M, Nguyen P, Fletterick R, Baxter JD, Webb P. (2005) Rearrangements in thyroid hormone receptor charge clusters that stabilize bound 3,5',5-triiodo-L-thyronine and inhibit homodimer formation. J Biol Chem. 280(27): 25665-73.

Vinogradova MV, Stone DB, Malanina GG, Karatzaferi C, Cooke R, Mendelson RA, Fletterick RJ. (2005) Ca2+-regulated structural changes in troponin. PNAS U S A. 2005 102(14): 5038-43.

Krylova I, Sablin EP, Moore J, Xu RX, Waitt GM Krylova I, Sablin EP, Moore J, Xu RX, Waitt GM, McKay A., Juzumiene D, Bynum JM, Montana V, Lebedeva L, Suzawa M, Williams JD, Williams SP, Guy RK, Thornton JW, Fletterick RJ,Willson TM, and HA Ingraham. (2005) Structural analyses reveal phosphatidyl inositols as ligands for the NR5 orphan receptors SF-1 and LRH-1. Cell 120: 343-355.

INDIVIDUAL PROJECTS

ACTIVE PROJECTS

PAST PROJECTS

PUBLICATIONS

Togashi M, Borngraeber S, Sandler B, Fletterick RJ, Webb P and Baxter JD (2004) Conformational adaptations of nuclear receptor ligand binding domains to agonists. Potential for novel approaches to ligand design. J. Steroid Biochem. Mol. Biol , 93, Issues 2-5 : 127-137.

Estébanez-Perpiñá E, Moore JM, Mar E, Rodrigues E, Nguyen P, Baxter J, Buehrer B,Webb P, Fletterick RJ and RK Guy (2004) The molecular mechanisms of coactivator utilization in ligand dependent transactivation by the androgen receptor. J Biol Chem.280(9): 8060-8.

Hur E, Pfaff S, Payne E, Gron H, Buehrer B, and RJ Fletterick. (2004) Accommodation at the androgen receptor coactivator binding interface. PLoS Biology, 2(9): e274.

Sandler B, Webb P, Apriletti JW, Huber R, Togashi M, Juric S, Nilsson S, Wagner R, Fletterick RJ, Baxter JD (2004) Thyroxine-Thyroid Hormone Receptor Interactions. J Biol Chem (in press)

Sandler BH, Baxter JD, and RJ Fletterick. (2004) Learning from nature's experiments on the thyroid hormone receptor: X-ray structures of RTH mutant ligand-binding domains. IN: Syndrome of Hormone Resistance on the Hypothalamic-Pituitary-Thyroid Axis. Ed., Paolo Beck-Peccoz. Kluwer Academic Publishers.

Ruggles SW, Fletterick RJ, Craik CS. (2004) Characterizing structural determinants of Granzyme B reveals potent mediators of extended substrate specificity. J Biol Chem. 279(29): 30751-9.

Shipley K, Hekmat-Nejad M, Turner J, Moores C, Anderson R, Milligan R, Sakowicz R, and RJ Fletterick. (2004) Structure of a kinesin microtubule depolymerization machine. EMBO J. 23(7): 1422-32

Vinogradova, M.V., Reddy, V.S., Reddy, A. S.N., Sablin, E.P., and R.J. Fletterick (2004) Crystal structure of kinesin regulated by Ca2+/calmodulin. J. Biol. Chem. 279(22): 23504-9.

Sablin EP, Fletterick RJ. (2004) Coordination between motor domains in processive kinesins. J Biol Chem. 279(16): 15707-10.

Waugh SM and Fletterick RJ. (2004) Crystallization and analysis of serine proteases with ecotin. Protein Crystallography in Drug Discovery 20: 171-186.

Borngraeber, S., Budny, M.J., Chiellini, G., Cunha Lima, S., Togashi, M.,Webb, P., Baxter, J., Scanlan, T., Fletterick , R.J.(2003) Ligand selectivity by seeking hydrophobicity in thyroid hormone receptor. PNAS 100(26): 15358-63.

Wang SX, Hur E, Sousa CA, Brinen L, Slivka EJ, Fletterick RJ. (2003) The extended interactions and Gla domain of blood coagulation factor Xa. Biochemistry 42(26): 7959-66.

Sablin, E.P., Krylova, I.N., Fletterick, R.J., and H.A. Ingraham (2003) A novel structural element accounts for the constitutive activity of the orphan nuclear receptor, LRH-1. Mol Cell. 11(6): 1575-85.

Bell JK, Goetz DH, Mahrus S, Harris JL, Fletterick RJ, Craik CS. (2003) The oligomeric structure of human granzyme A is a determinant of its extended substrate specificity. Nat Struct Biol. 10(7): 527-34.

Huber BR, Desclozeaux M, West BL, Cunha-Lima ST, Nguyen HT, Baxter JD, Ingraham HA, Fletterick RJ. (2003) Thyroid hormone receptor-beta mutations conferring hormone resistance and reduced corepressor release exhibit decreased stability in the N-terminal ligand-binding domain. Mol Endo. 17(1):107-16.

Huber BR, Sandler B, West BL, Cunha Lima ST, Nguyen HT, Apriletti JW, Baxter JD, Fletterick RJ. (2003) Resistance to thyroid hormone mutants with impaired hormone binding. Mol Endo. 17(4): 643-52.

Webb P, Nguyen NH, Chiellini G, Yoshihara HA, Cunha Lima ST, Apriletti JW, Ribeiro RC, Marimuthu A, West BL, Goede P, Mellstrom K, Nilsson S, Kushner PJ, Fletterick RJ, Scanlan TS, Baxter JD. (2002) Design of thyroid hormone receptor antagonists from first principles. J Steroid Biochem Mol Biol. 83(1-5): 59-73. Review.

Sindelar CV, Budny MJ, Rice S, Naber N, Fletterick R, and Cooke R.(2002) Two conformations in the human kinesin powerstroke defined by X-ray crystallography and EPR spectroscopy. Nature Structural Biology 9(11): 844-8.

Dawson JF, Sablin EP, Spudich JA, Fletterick RJ. (2003) Structure of an F-actin trimer disrupted by gelsolin and implications for the mechanism of severing. J Biol Chem. 278(2): 1229-38.

Sablin EP, Dawson JF, VanLoock MS, Spudich JA, Egelman EH, Fletterick RJ. (2002) How does ATP hydrolysis control actin's associations? Proc Natl Acad Sci U S A. 99(17): 10945-7.

Walther M, Anton M, Wiedmann M, Fletterick R, Kuhn H. (2002) The N-terminal domain of the reticulocyte-type 15-lipoxygenase is not essential for enzymatic activity but contains determinants for membrane binding. J Biol Chem. 277(30): 27360-6.

Laboissiere MC, Young MM, Pinho RG, Todd S, Fletterick RJ, Kuntz I, Craik CS. (2002) Computer assisted mutagenesis of ecotin to engineer its secondary binding site for urokinase inhibition. J Biol Chem. 277(29): 26623-31.

Marimuthu A, Feng W, Tagami T, Nguyen H, Jameson JL, Fletterick RJ, Baxter, JD, West BL. (2002) TR surfaces and conformations required to bind nuclear receptor corepressor. Mol Endocrinol. 16(2): 271-86.

Baxter, JD, Goede, P., Apriletti, J.W., West, B.L., Feng W., Mellstrom K., Fletterick, R.J., Wagner, R.L., Kushner, P.J., Ribeiro, R.C.J., Webb, P., Scanlan, T.S. and S. Nilsson. (2002) Structure-based design and synthesis of a thyroid hormone receptor (TR) antagonist. Endocrinology 143(2): 517-524.

Sablin EP, Fletterick RJ. (2002) Nucleotide switches in molecular motors: structural analysis of kinesins and myosins. Curr Opin Struct Biol. 11(6): 716-24. Review.

Baxter JD, Dillmann WH, West BL, Huber R, Furlow JD, Fletterick RJ, Webb P, Apriletti JW, Scanlan TS. (2001) Selective modulation of thyroid hormone receptor action. J Steroid Biochem Mol Biol. 76(1-5): 31-42. Review.

Wang, S.X., Esmon, C.T., and R.J. Fletterick. (2001) Crystal structure of thrombin-ecotin reveals conformational changes and extended interactions. Biochem. 40(34): 10038-10046.

Turner, J., Anderson, R., Guo, J., Beraud, J., Fletterick, R., Sakowicz, R.. (2001) Crystal structure of the mitotic spindle kinesin Eg5 reveals a novel conformation of the neck-linker. J. Biol. Chem 276: 25496-25502.

Kikkawa, M., Sablin, E.P., Okada, Y., Yajima, H., Fletterick R.J. and N. Hirokawa. (2001) Switch-based mechanism of kinesin motors. Nature 411(6836): 439-45.

Sindelar CV, Rice S, Fletterick R, et al. (2001) EPR studies suggest that a crystallized conformation of kinesin resembles the ATP-bound, microtubule-bound intermediate. Biophys J 80(1): 2577.

Ribeiro RCJ, Feng W, Wagner RL, Costa CHRM, Pereira AC, Apriletti JW, Fletterick RJ, Baxter JD. (2001) Definition of the surface in the thyroid hormone receptor ligand binding domain for association as homodimers and heterodimers with retinoid X receptor. J. Biol. Chem. 276(18): 14987-95.

Eggers CT, Wang SX, Fletterick RJ, Craik CS. (2001) The role of ecotin dimerization in protease inhibition. J Mol Biol. 308(5): 975-91.

Baxter JD, Dillmann WH, West BL, Huber R, Furlow JD, Fletterick RJ, Webb P, Apriletti JW, Scanlan TS. (2001) Selective modulation of thyroid hormone receptor action. J  Steroid Biochem Mol Biol. 76(1-5): 31-42. Review.

Wagner, R.L., Shiau, A.K., Huber, B.R., Kelly, A., Scanlan, T.S., Apriletti, J.W., West, B.L., Baxter, J.D., and R.J. Fletterick. (2000) Hormone selectivity in thyroid hormone receptors. Molec. Endocrinology 15(3): 398-410.