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The nuclear receptor superfamily: A structural perspective.

Weikum ER, Liu X, Ortlund EA.

Protein Sci. 2018 Aug 15. doi: 10.1002/pro.3496. [Epub ahead of print] Review.


Delimiting the autoinhibitory module of von Willebrand factor.

Deng W, Voos KM, Colucci JK, Legan ER, Ortlund EA, Lollar P, Li R.

J Thromb Haemost. 2018 Jul 27. doi: 10.1111/jth.14251. [Epub ahead of print]


Caspase-8 Collaborates with Caspase-11 to Drive Tissue Damage and Execution of Endotoxic Shock.

Mandal P, Feng Y, Lyons JD, Berger SB, Otani S, DeLaney A, Tharp GK, Maner-Smith K, Burd EM, Schaeffer M, Hoffman S, Capriotti C, Roback L, Young CB, Liang Z, Ortlund EA, DiPaolo NC, Bosinger S, Bertin J, Gough PJ, Brodsky IE, Coopersmith CM, Shayakhmetov DM, Mocarski ES.

Immunity. 2018 Jul 17;49(1):42-55.e6. doi: 10.1016/j.immuni.2018.06.011.


Cryptic glucocorticoid receptor-binding sites pervade genomic NF-κB response elements.

Hudson WH, Vera IMS, Nwachukwu JC, Weikum ER, Herbst AG, Yang Q, Bain DL, Nettles KW, Kojetin DJ, Ortlund EA.

Nat Commun. 2018 Apr 6;9(1):1337. doi: 10.1038/s41467-018-03780-1.


Structural and Dynamics Comparison of Thermostability in Ancient, Modern, and Consensus Elongation Factor Tus.

Okafor CD, Pathak MC, Fagan CE, Bauer NC, Cole MF, Gaucher EA, Ortlund EA.

Structure. 2018 Jan 2;26(1):118-129.e3. doi: 10.1016/j.str.2017.11.018. Epub 2017 Dec 21.


Nucleotide Binding to ARL2 in the TBCD∙ARL2∙β-Tubulin Complex Drives Conformational Changes in β-Tubulin.

Francis JW, Goswami D, Novick SJ, Pascal BD, Weikum ER, Ortlund EA, Griffin PR, Kahn RA.

J Mol Biol. 2017 Nov 24;429(23):3696-3716. doi: 10.1016/j.jmb.2017.09.016. Epub 2017 Sep 29.


Tethering not required: the glucocorticoid receptor binds directly to activator protein-1 recognition motifs to repress inflammatory genes.

Weikum ER, de Vera IMS, Nwachukwu JC, Hudson WH, Nettles KW, Kojetin DJ, Ortlund EA.

Nucleic Acids Res. 2017 Aug 21;45(14):8596-8608. doi: 10.1093/nar/gkx509.


Structural Analysis of the Glucocorticoid Receptor Ligand-Binding Domain in Complex with Triamcinolone Acetonide and a Fragment of the Atypical Coregulator, Small Heterodimer Partner.

Weikum ER, Okafor CD, D'Agostino EH, Colucci JK, Ortlund EA.

Mol Pharmacol. 2017 Jul;92(1):12-21. doi: 10.1124/mol.117.108506. Epub 2017 Apr 10.


Structure and Dynamics of the Liver Receptor Homolog 1-PGC1α Complex.

Mays SG, Okafor CD, Tuntland ML, Whitby RJ, Dharmarajan V, Stec J, Griffin PR, Ortlund EA.

Mol Pharmacol. 2017 Jul;92(1):1-11. doi: 10.1124/mol.117.108514. Epub 2017 Mar 31.


Glucocorticoid receptor control of transcription: precision and plasticity via allostery.

Weikum ER, Knuesel MT, Ortlund EA, Yamamoto KR.

Nat Rev Mol Cell Biol. 2017 Mar;18(3):159-174. doi: 10.1038/nrm.2016.152. Epub 2017 Jan 5. Review.


A Structural Investigation into Oct4 Regulation by Orphan Nuclear Receptors, Germ Cell Nuclear Factor (GCNF), and Liver Receptor Homolog-1 (LRH-1).

Weikum ER, Tuntland ML, Murphy MN, Ortlund EA.

J Mol Biol. 2016 Dec 4;428(24 Pt B):4981-4992. doi: 10.1016/j.jmb.2016.10.025. Epub 2016 Oct 27.


Crystal Structures of the Nuclear Receptor, Liver Receptor Homolog 1, Bound to Synthetic Agonists.

Mays SG, Okafor CD, Whitby RJ, Goswami D, Stec J, Flynn AR, Dugan MC, Jui NT, Griffin PR, Ortlund EA.

J Biol Chem. 2016 Dec 2;291(49):25281-25291. Epub 2016 Sep 30.


Distal substitutions drive divergent DNA specificity among paralogous transcription factors through subdivision of conformational space.

Hudson WH, Kossmann BR, de Vera IM, Chuo SW, Weikum ER, Eick GN, Thornton JW, Ivanov IN, Kojetin DJ, Ortlund EA.

Proc Natl Acad Sci U S A. 2016 Jan 12;113(2):326-31. doi: 10.1073/pnas.1518960113. Epub 2015 Dec 29.


Unexpected Allosteric Network Contributes to LRH-1 Co-regulator Selectivity.

Musille PM, Kossmann BR, Kohn JA, Ivanov I, Ortlund EA.

J Biol Chem. 2016 Jan 15;291(3):1411-26. doi: 10.1074/jbc.M115.662874. Epub 2015 Nov 9.


Identification of a lipid scrambling domain in ANO6/TMEM16F.

Yu K, Whitlock JM, Lee K, Ortlund EA, Cui YY, Hartzell HC.

Elife. 2015 Jun 9;4:e06901. doi: 10.7554/eLife.06901.


Integration of G protein α (Gα) signaling by the regulator of G protein signaling 14 (RGS14).

Brown NE, Goswami D, Branch MR, Ramineni S, Ortlund EA, Griffin PR, Hepler JR.

J Biol Chem. 2015 Apr 3;290(14):9037-49. doi: 10.1074/jbc.M114.634329. Epub 2015 Feb 9.


Aging. Lysosomal signaling molecules regulate longevity in Caenorhabditis elegans.

Folick A, Oakley HD, Yu Y, Armstrong EH, Kumari M, Sanor L, Moore DD, Ortlund EA, Zechner R, Wang MC.

Science. 2015 Jan 2;347(6217):83-6. doi: 10.1126/science.1258857.


Conserved sequence-specific lincRNA-steroid receptor interactions drive transcriptional repression and direct cell fate.

Hudson WH, Pickard MR, de Vera IM, Kuiper EG, Mourtada-Maarabouni M, Conn GL, Kojetin DJ, Williams GT, Ortlund EA.

Nat Commun. 2014 Nov 7;5:5395. doi: 10.1038/ncomms6395.


The structure, function and evolution of proteins that bind DNA and RNA.

Hudson WH, Ortlund EA.

Nat Rev Mol Cell Biol. 2014 Nov;15(11):749-60. doi: 10.1038/nrm3884. Epub 2014 Oct 1. Review.


Evolution of DNA specificity in a transcription factor family produced a new gene regulatory module.

McKeown AN, Bridgham JT, Anderson DW, Murphy MN, Ortlund EA, Thornton JW.

Cell. 2014 Sep 25;159(1):58-68. doi: 10.1016/j.cell.2014.09.003.


Crystal structure of the mineralocorticoid receptor DNA binding domain in complex with DNA.

Hudson WH, Youn C, Ortlund EA.

PLoS One. 2014 Sep 4;9(9):e107000. doi: 10.1371/journal.pone.0107000. eCollection 2014.


Structural basis for ligand regulation of the fatty acid-binding protein 5, peroxisome proliferator-activated receptor β/δ (FABP5-PPARβ/δ) signaling pathway.

Armstrong EH, Goswami D, Griffin PR, Noy N, Ortlund EA.

J Biol Chem. 2014 May 23;289(21):14941-54. doi: 10.1074/jbc.M113.514646. Epub 2014 Apr 1.


Identification of a small molecular insulin receptor agonist with potent antidiabetes activity.

Qiang G, Xue S, Yang JJ, Du G, Pang X, Li X, Goswami D, Griffin PR, Ortlund EA, Chan CB, Ye K.

Diabetes. 2014 Apr;63(4):1394-409. doi: 10.2337/db13-0334.


Evolutionary history and metabolic insights of ancient mammalian uricases.

Kratzer JT, Lanaspa MA, Murphy MN, Cicerchi C, Graves CL, Tipton PA, Ortlund EA, Johnson RJ, Gaucher EA.

Proc Natl Acad Sci U S A. 2014 Mar 11;111(10):3763-8. doi: 10.1073/pnas.1320393111. Epub 2014 Feb 18.


Estrogen receptor α polymorphism in a species with alternative behavioral phenotypes.

Horton BM, Hudson WH, Ortlund EA, Shirk S, Thomas JW, Young ER, Zinzow-Kramer WM, Maney DL.

Proc Natl Acad Sci U S A. 2014 Jan 28;111(4):1443-8. doi: 10.1073/pnas.1317165111. Epub 2014 Jan 13.


Vestigialization of an allosteric switch: genetic and structural mechanisms for the evolution of constitutive activity in a steroid hormone receptor.

Bridgham JT, Keay J, Ortlund EA, Thornton JW.

PLoS Genet. 2014 Jan;10(1):e1004058. doi: 10.1371/journal.pgen.1004058. Epub 2014 Jan 9.


A phosphatidylinositol transfer protein integrates phosphoinositide signaling with lipid droplet metabolism to regulate a developmental program of nutrient stress-induced membrane biogenesis.

Ren J, Pei-Chen Lin C, Pathak MC, Temple BR, Nile AH, Mousley CJ, Duncan MC, Eckert DM, Leiker TJ, Ivanova PT, Myers DS, Murphy RC, Brown HA, Verdaasdonk J, Bloom KS, Ortlund EA, Neiman AM, Bankaitis VA.

Mol Biol Cell. 2014 Mar;25(5):712-27. doi: 10.1091/mbc.E13-11-0634. Epub 2014 Jan 8.


Expression, purification and crystallization of the ancestral androgen receptor-DHT complex.

Colucci JK, Ortlund EA.

Acta Crystallogr Sect F Struct Biol Cryst Commun. 2013 Sep;69(Pt 9):994-6. doi: 10.1107/S1744309113018745. Epub 2013 Aug 19.


Biophysical mechanisms for large-effect mutations in the evolution of steroid hormone receptors.

Harms MJ, Eick GN, Goswami D, Colucci JK, Griffin PR, Ortlund EA, Thornton JW.

Proc Natl Acad Sci U S A. 2013 Jul 9;110(28):11475-80. doi: 10.1073/pnas.1303930110. Epub 2013 Jun 24.


Divergent sequence tunes ligand sensitivity in phospholipid-regulated hormone receptors.

Musille PM, Pathak M, Lauer JL, Griffin PR, Ortlund EA.

J Biol Chem. 2013 Jul 12;288(28):20702-12. doi: 10.1074/jbc.M113.472837. Epub 2013 Jun 4.


Phospholipid--driven gene regulation.

Musille PM, Kohn JA, Ortlund EA.

FEBS Lett. 2013 Apr 17;587(8):1238-46. doi: 10.1016/j.febslet.2013.01.004. Epub 2013 Jan 16. Review.


Hydrophobic environment is a key factor for the stability of thermophilic proteins.

Gromiha MM, Pathak MC, Saraboji K, Ortlund EA, Gaucher EA.

Proteins. 2013 Apr;81(4):715-21. doi: 10.1002/prot.24232. Epub 2013 Jan 15.


The structural basis of direct glucocorticoid-mediated transrepression.

Hudson WH, Youn C, Ortlund EA.

Nat Struct Mol Biol. 2013 Jan;20(1):53-8. doi: 10.1038/nsmb.2456. Epub 2012 Dec 9.


Evolution of minimal specificity and promiscuity in steroid hormone receptors.

Eick GN, Colucci JK, Harms MJ, Ortlund EA, Thornton JW.

PLoS Genet. 2012;8(11):e1003072. doi: 10.1371/journal.pgen.1003072. Epub 2012 Nov 15.


Discovery of a new class of liver receptor homolog-1 (LRH-1) antagonists: virtual screening, synthesis and biological evaluation.

Rey J, Hu H, Kyle F, Lai CF, Buluwela L, Coombes RC, Ortlund EA, Ali S, Snyder JP, Barrett AG.

ChemMedChem. 2012 Nov;7(11):1909-14. doi: 10.1002/cmdc.201200307. Epub 2012 Sep 7.


Antidiabetic phospholipid-nuclear receptor complex reveals the mechanism for phospholipid-driven gene regulation.

Musille PM, Pathak M, Lauer JL, Hudson WH, Griffin PR, Ortlund EA.

Nat Struct Mol Biol. 2012 Apr 15;19(5):532-S2. doi: 10.1038/nsmb.2279.


Deciphering modern glucocorticoid cross-pharmacology using ancestral corticosteroid receptors.

Kohn JA, Deshpande K, Ortlund EA.

J Biol Chem. 2012 May 11;287(20):16267-75. doi: 10.1074/jbc.M112.346411. Epub 2012 Mar 21.


Crystallization and preliminary X-ray diffraction analysis of Sfh3, a member of the Sec14 protein superfamily.

Ren J, Schaaf G, Bankaitis VA, Ortlund EA, Pathak MC.

Acta Crystallogr Sect F Struct Biol Cryst Commun. 2011 Oct 1;67(Pt 10):1239-43. doi: 10.1107/S1744309111027096. Epub 2011 Sep 29.


Mechanisms for the evolution of a derived function in the ancestral glucocorticoid receptor.

Carroll SM, Ortlund EA, Thornton JW.

PLoS Genet. 2011 Jun;7(6):e1002117. doi: 10.1371/journal.pgen.1002117. Epub 2011 Jun 16.


A nuclear-receptor-dependent phosphatidylcholine pathway with antidiabetic effects.

Lee JM, Lee YK, Mamrosh JL, Busby SA, Griffin PR, Pathak MC, Ortlund EA, Moore DD.

Nature. 2011 May 25;474(7352):506-10. doi: 10.1038/nature10111.


Resurrection of a functional phosphatidylinositol transfer protein from a pseudo-Sec14 scaffold by directed evolution.

Schaaf G, Dynowski M, Mousley CJ, Shah SD, Yuan P, Winklbauer EM, de Campos MK, Trettin K, Quinones MC, Smirnova TI, Yanagisawa LL, Ortlund EA, Bankaitis VA.

Mol Biol Cell. 2011 Mar 15;22(6):892-905. doi: 10.1091/mbc.E10-11-0903. Epub 2011 Jan 19.


Protein evolution by molecular tinkering: diversification of the nuclear receptor superfamily from a ligand-dependent ancestor.

Bridgham JT, Eick GN, Larroux C, Deshpande K, Harms MJ, Gauthier ME, Ortlund EA, Degnan BM, Thornton JW.

PLoS Biol. 2010 Oct 5;8(10). pii: e1000497. doi: 10.1371/journal.pbio.1000497.


The liver receptor homolog-1 regulates estrogen receptor expression in breast cancer cells.

Thiruchelvam PT, Lai CF, Hua H, Thomas RS, Hurtado A, Hudson W, Bayly AR, Kyle FJ, Periyasamy M, Photiou A, Spivey AC, Ortlund EA, Whitby RJ, Carroll JS, Coombes RC, Buluwela L, Ali S.

Breast Cancer Res Treat. 2011 Jun;127(2):385-96. doi: 10.1007/s10549-010-0994-9. Epub 2010 Jul 6.


Reconstructed evolutionary adaptive paths give polymerases accepting reversible terminators for sequencing and SNP detection.

Chen F, Gaucher EA, Leal NA, Hutter D, Havemann SA, Govindarajan S, Ortlund EA, Benner SA.

Proc Natl Acad Sci U S A. 2010 Feb 2;107(5):1948-53. doi: 10.1073/pnas.0908463107. Epub 2010 Jan 11.


An epistatic ratchet constrains the direction of glucocorticoid receptor evolution.

Bridgham JT, Ortlund EA, Thornton JW.

Nature. 2009 Sep 24;461(7263):515-9. doi: 10.1038/nature08249.


Functional anatomy of phospholipid binding and regulation of phosphoinositide homeostasis by proteins of the sec14 superfamily.

Schaaf G, Ortlund EA, Tyeryar KR, Mousley CJ, Ile KE, Garrett TA, Ren J, Woolls MJ, Raetz CR, Redinbo MR, Bankaitis VA.

Mol Cell. 2008 Feb 1;29(2):191-206. doi: 10.1016/j.molcel.2007.11.026.


Crystal structure of an ancient protein: evolution by conformational epistasis.

Ortlund EA, Bridgham JT, Redinbo MR, Thornton JW.

Science. 2007 Sep 14;317(5844):1544-8. Epub 2007 Aug 16.


Structural features of the ligand binding site on human complement protein C8gamma: a member of the lipocalin family.

Chiswell B, Lovelace LL, Brannen C, Ortlund EA, Lebioda L, Sodetz JM.

Biochim Biophys Acta. 2007 May;1774(5):637-44. Epub 2007 Mar 20.


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