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Monomeric complex of human orphan estrogen related receptor-2 with DNA: a pseudo-dimer interface mediates extended half-site recognition.

Gearhart MD, Holmbeck SM, Evans RM, Dyson HJ, Wright PE
J Mol Biol 327 819-32 (2003)
Cited: 69 times
EuropePMC logo PMID: 12654265

Abstract

While most nuclear receptors bind DNA as homo or heterodimers, the human estrogen related receptors (hERRs) are members of a subfamily of orphan receptors that bind DNA as monomers. We have determined the solution structure of the DNA binding domain (DBD) of hERR2 bound to its cognate DNA. The structure and base interactions of the core DBD are similar to those of other nuclear receptors. However, high-affinity, sequence-specific DNA binding as a monomer necessitates formation of additional base contacts outside the core DBD. This is accomplished using a modified guanosine-binding "AT-hook" within the C-terminal extension (CTE) flanking the DBD, which makes base-specific minor groove interactions. The structure of the CTE is stabilized both by interactions with the DNA and by packing against a region of the core DBD normally reserved for dimerization. This pseudo-dimer interface provides a basis for the expansion of DNA recognition and suggests a mechanism through which dimerization may have evolved from an ancestral monomeric receptor.

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  1. Estrogen-related receptor β (ERRβ) - renaissance receptor or receptor renaissance? Divekar SD, Tiek DM, Fernandez A, Riggins RB. Nucl Recept Signal 14 e002 (2016)

Articles - 1lo1 mentioned but not cited (6)

  1. Extent of structural asymmetry in homodimeric proteins: prevalence and relevance. Swapna LS, Srikeerthana K, Srinivasan N. PLoS One 7 e36688 (2012)
  2. Exploring DNA structure with Cn3D. Porter SG, Day J, McCarty RE, Shearn A, Shingles R, Fletcher L, Murphy S, Pearlman R. CBE Life Sci Educ 6 65-73 (2007)
  3. Obesity-induced protein carbonylation in murine adipose tissue regulates the DNA-binding domain of nuclear zinc finger proteins. Hauck AK, Zhou T, Hahn W, Petegrosso R, Kuang R, Chen Y, Bernlohr DA. J Biol Chem 293 13464-13476 (2018)
  4. The dipeptidyl peptidase IV inhibitors vildagliptin and K-579 inhibit a phospholipase C: a case of promiscuous scaffolds in proteins. Chakraborty S, Rendón-Ramírez A, Ásgeirsson B, Dutta M, Ghosh AS, Oda M, Venkatramani R, Rao BJ, Dandekar AM, Goñi FM. F1000Res 2 286 (2013)
  5. A novel missense variant in ESRRB gene causing autosomal recessive non-syndromic hearing loss: in silico analysis of a case. Ghasemnejad T, Shekari Khaniani M, Nouri Nojadeh J, Mansoori Derakhshan S. BMC Med Genomics 15 18 (2022)
  6. Asymmetric dimerization in a transcription factor superfamily is promoted by allosteric interactions with DNA. Patel AKM, Vilela P, Shaik TB, McEwen AG, Hazemann I, Brillet K, Ennifar E, Hamiche A, Markov GV, Laudet V, Moras D, Klaholz BP, Billas IML. Nucleic Acids Res 51 8864-8879 (2023)


Reviews citing this publication (21)

  1. Structure-function relationship of estrogen receptor alpha and beta: impact on human health. Ascenzi P, Bocedi A, Marino M. Mol Aspects Med 27 299-402 (2006)
  2. Nuclear receptor structure: implications for function. Bain DL, Heneghan AF, Connaghan-Jones KD, Miura MT. Annu Rev Physiol 69 201-220 (2007)
  3. The NR3B subgroup: an ovERRview. Tremblay AM, Giguère V. Nucl Recept Signal 5 e009 (2007)
  4. Looking at nuclear receptors from a new angle. Helsen C, Claessens F. Mol Cell Endocrinol 382 97-106 (2014)
  5. Structural basis for nuclear hormone receptor DNA binding. Helsen C, Kerkhofs S, Clinckemalie L, Spans L, Laurent M, Boonen S, Vanderschueren D, Claessens F. Mol Cell Endocrinol 348 411-417 (2012)
  6. General molecular biology and architecture of nuclear receptors. Pawlak M, Lefebvre P, Staels B. Curr Top Med Chem 12 486-504 (2012)
  7. Roles of intrinsic disorder in protein-nucleic acid interactions. Dyson HJ. Mol Biosyst 8 97-104 (2012)
  8. Structural and functional analysis of domains of the progesterone receptor. Hill KK, Roemer SC, Churchill ME, Edwards DP. Mol Cell Endocrinol 348 418-429 (2012)
  9. The extended arms of DNA-binding domains: a tale of tails. Crane-Robinson C, Dragan AI, Privalov PL. Trends Biochem Sci 31 547-552 (2006)
  10. Regulation of gene expression with pyrrole-imidazole polyamides. Melander C, Burnett R, Gottesfeld JM. J Biotechnol 112 195-220 (2004)
  11. Advances in our structural understanding of orphan nuclear receptors. Gallastegui N, Mackinnon JA, Fletterick RJ, Estébanez-Perpiñá E. Trends Biochem Sci 40 25-35 (2015)
  12. Orphan nuclear receptors in breast cancer pathogenesis and therapeutic response. Riggins RB, Mazzotta MM, Maniya OZ, Clarke R. Endocr Relat Cancer 17 R213-31 (2010)
  13. Versatility or promiscuity: the estrogen receptors, control of ligand selectivity and an update on subtype selective ligands. Ng HW, Perkins R, Tong W, Hong H. Int J Environ Res Public Health 11 8709-8742 (2014)
  14. Cholesterol as an Endogenous ERRα Agonist: A New Perspective to Cancer Treatment. Casaburi I, Chimento A, De Luca A, Nocito M, Sculco S, Avena P, Trotta F, Rago V, Sirianni R, Pezzi V. Front Endocrinol (Lausanne) 9 525 (2018)
  15. Esrrb, an estrogen-related receptor involved in early development, pluripotency, and reprogramming. Festuccia N, Owens N, Navarro P. FEBS Lett 592 852-877 (2018)
  16. ERRα as a Bridge Between Transcription and Function: Role in Liver Metabolism and Disease. Xia H, Dufour CR, Giguère V. Front Endocrinol (Lausanne) 10 206 (2019)
  17. Emerging Roles of Estrogen-Related Receptors in the Brain: Potential Interactions with Estrogen Signaling. Saito K, Cui H. Int J Mol Sci 19 (2018)
  18. Bisphenols and Leydig Cell Development and Function. Li X, Wen Z, Wang Y, Mo J, Zhong Y, Ge RS. Front Endocrinol (Lausanne) 11 447 (2020)
  19. Expression and function of estrogen receptors and estrogen-related receptors in the brain and their association with Alzheimer's disease. Sato K, Takayama KI, Inoue S. Front Endocrinol (Lausanne) 14 1220150 (2023)
  20. International Union of Basic and Clinical Pharmacology CXIII: Nuclear Receptor Superfamily-Update 2023. Burris TP, de Vera IMS, Cote I, Flaveny CA, Wanninayake US, Chatterjee A, Walker JK, Steinauer N, Zhang J, Coons LA, Korach KS, Cain DW, Hollenberg AN, Webb P, Forrest D, Jetten AM, Edwards DP, Grimm SL, Hartig S, Lange CA, Richer JK, Sartorius CA, Tetel M, Billon C, Elgendy B, Hegazy L, Griffett K, Peinetti N, Burnstein KL, Hughes TS, Sitaula S, Stayrook KR, Culver A, Murray MH, Finck BN, Cidlowski JA. Pharmacol Rev 75 1233-1318 (2023)
  21. The emerging role of estrogen related receptorα in complications of non-small cell lung cancers. Mukherjee TK, Malik P, Hoidal JR. Oncol Lett 21 258 (2021)

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  1. The role of DNA shape in protein-DNA recognition. Rohs R, West SM, Sosinsky A, Liu P, Mann RS, Honig B. Nature 461 1248-1253 (2009)
  2. Functional specificity of a Hox protein mediated by the recognition of minor groove structure. Joshi R, Passner JM, Rohs R, Jain R, Sosinsky A, Crickmore MA, Jacob V, Aggarwal AK, Honig B, Mann RS. Cell 131 530-543 (2007)
  3. Estrogen-related receptor beta interacts with Oct4 to positively regulate Nanog gene expression. van den Berg DL, Zhang W, Yates A, Engelen E, Takacs K, Bezstarosti K, Demmers J, Chambers I, Poot RA. Mol Cell Biol 28 5986-5995 (2008)
  4. Structural basis for cooperative transcription factor binding to the CBP coactivator. De Guzman RN, Goto NK, Dyson HJ, Wright PE. J Mol Biol 355 1005-1013 (2006)
  5. An acetylation switch modulates the transcriptional activity of estrogen-related receptor alpha. Wilson BJ, Tremblay AM, Deblois G, Sylvain-Drolet G, Giguère V. Mol Endocrinol 24 1349-1358 (2010)
  6. Expanding the proteome: disordered and alternatively folded proteins. Dyson HJ. Q Rev Biophys 44 467-518 (2011)
  7. A comprehensive view of nuclear receptor cancer cistromes. Tang Q, Chen Y, Meyer C, Geistlinger T, Lupien M, Wang Q, Liu T, Zhang Y, Brown M, Liu XS. Cancer Res 71 6940-6947 (2011)
  8. Mitotic binding of Esrrb marks key regulatory regions of the pluripotency network. Festuccia N, Dubois A, Vandormael-Pournin S, Gallego Tejeda E, Mouren A, Bessonnard S, Mueller F, Proux C, Cohen-Tannoudji M, Navarro P. Nat Cell Biol 18 1139-1148 (2016)
  9. Structure of the progesterone receptor-deoxyribonucleic acid complex: novel interactions required for binding to half-site response elements. Roemer SC, Donham DC, Sherman L, Pon VH, Edwards DP, Churchill ME. Mol Endocrinol 20 3042-3052 (2006)
  10. Decreased recognition of SUMO-sensitive target genes following modification of SF-1 (NR5A1). Campbell LA, Faivre EJ, Show MD, Ingraham JG, Flinders J, Gross JD, Ingraham HA. Mol Cell Biol 28 7476-7486 (2008)
  11. The role of the C-terminal extension (CTE) of the estrogen receptor alpha and beta DNA binding domain in DNA binding and interaction with HMGB. Melvin VS, Harrell C, Adelman JS, Kraus WL, Churchill M, Edwards DP. J Biol Chem 279 14763-14771 (2004)
  12. A single nucleotide in an estrogen-related receptor alpha site can dictate mode of binding and peroxisome proliferator-activated receptor gamma coactivator 1alpha activation of target promoters. Barry JB, Laganière J, Giguère V. Mol Endocrinol 20 302-310 (2006)
  13. A progesterone receptor co-activator (JDP2) mediates activity through interaction with residues in the carboxyl-terminal extension of the DNA binding domain. Hill KK, Roemer SC, Jones DN, Churchill ME, Edwards DP. J Biol Chem 284 24415-24424 (2009)
  14. Crystal structure of the human LRH-1 DBD-DNA complex reveals Ftz-F1 domain positioning is required for receptor activity. Solomon IH, Hager JM, Safi R, McDonnell DP, Redinbo MR, Ortlund EA. J Mol Biol 354 1091-1102 (2005)
  15. Co-motif discovery identifies an Esrrb-Sox2-DNA ternary complex as a mediator of transcriptional differences between mouse embryonic and epiblast stem cells. Hutchins AP, Choo SH, Mistri TK, Rahmani M, Woon CT, Ng CK, Jauch R, Robson P. Stem Cells 31 269-281 (2013)
  16. Expression and ecdysteroid responsiveness of the nuclear receptors HR3 and E75 in the crustacean Daphnia magna. Hannas BR, LeBlanc GA. Mol Cell Endocrinol 315 208-218 (2010)
  17. Mechanism of high-mobility group protein B enhancement of progesterone receptor sequence-specific DNA binding. Roemer SC, Adelman J, Churchill ME, Edwards DP. Nucleic Acids Res 36 3655-3666 (2008)
  18. A candidate juvenoid hormone receptor cis-element in the Daphnia magna hb2 hemoglobin gene promoter. Gorr TA, Rider CV, Wang HY, Olmstead AW, LeBlanc GA. Mol Cell Endocrinol 247 91-102 (2006)
  19. CTCF confers local nucleosome resiliency after DNA replication and during mitosis. Owens N, Papadopoulou T, Festuccia N, Tachtsidi A, Gonzalez I, Dubois A, Vandormael-Pournin S, Nora EP, Bruneau BG, Cohen-Tannoudji M, Navarro P. Elife 8 (2019)
  20. Communication between the ERRalpha homodimer interface and the PGC-1alpha binding surface via the helix 8-9 loop. Greschik H, Althage M, Flaig R, Sato Y, Chavant V, Peluso-Iltis C, Choulier L, Cronet P, Rochel N, Schüle R, Strömstedt PE, Moras D. J Biol Chem 283 20220-20230 (2008)
  21. The plasticity of estrogen receptor-DNA complexes: binding affinity and specificity of estrogen receptors to estrogen response element half-sites separated by variant spacers. El Marzouk S, Gahattamaneni R, Joshi SR, Scovell WM. J Steroid Biochem Mol Biol 110 186-195 (2008)
  22. Structure of a thyroid hormone receptor DNA-binding domain homodimer bound to an inverted palindrome DNA response element. Chen Y, Young MA. Mol Endocrinol 24 1650-1664 (2010)
  23. Kaiso uses all three zinc fingers and adjacent sequence motifs for high affinity binding to sequence-specific and methyl-CpG DNA targets. Buck-Koehntop BA, Martinez-Yamout MA, Dyson HJ, Wright PE. FEBS Lett 586 734-739 (2012)
  24. BmCbZ, an insect-specific factor featuring a composite DNA-binding domain, interacts with BmC/EBPgamma. Sourmeli S, Papantonis A, Lecanidou R. Biochem Biophys Res Commun 338 1957-1965 (2005)
  25. 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 428 4981-4992 (2016)
  26. Estrogen-related receptor β deficiency alters body composition and response to restraint stress. Byerly MS, Swanson RD, Wong GW, Blackshaw S. BMC Physiol 13 10 (2013)
  27. Antimitotic activity of DY131 and the estrogen-related receptor beta 2 (ERRβ2) splice variant in breast cancer. Heckler MM, Zeleke TZ, Divekar SD, Fernandez AI, Tiek DM, Woodrick J, Farzanegan A, Roy R, Üren A, Mueller SC, Riggins RB. Oncotarget 7 47201-47220 (2016)
  28. Structural insights into Estrogen Related Receptor-β modulation: 4-methylenesterols from Theonella swinhoei sponge as the first example of marine natural antagonists. Di Micco S, Renga B, Carino A, D'Auria MV, Zampella A, Riccio R, Fiorucci S, Bifulco G. Steroids 80 51-63 (2014)
  29. Induced folding in RNA recognition by Arabidopsis thaliana DCL1. Suarez IP, Burdisso P, Benoit MP, Boisbouvier J, Rasia RM. Nucleic Acids Res 43 6607-6619 (2015)
  30. Increased expression of estrogen-related receptor β during adaptation of adult cardiomyocytes to sustained hypoxia. Cunningham KF, Beeson GC, Beeson CC, McDermott PJ. Am J Cardiovasc Dis 6 46-54 (2016)
  31. Importance of the Sequence-Directed DNA Shape for Specific Binding Site Recognition by the Estrogen-Related Receptor. Mohideen-Abdul K, Tazibt K, Bourguet M, Hazemann I, Lebars I, Takacs M, Cianférani S, Klaholz BP, Moras D, Billas IML. Front Endocrinol (Lausanne) 8 140 (2017)
  32. Fluorescence Anisotropy-Based Tethering for Discovery of Protein-Protein Interaction Stabilizers. Sijbesma E, Somsen BA, Miley GP, Leijten-van de Gevel IA, Brunsveld L, Arkin MR, Ottmann C. ACS Chem Biol 15 3143-3148 (2020)
  33. Structural overview and perspectives of the nuclear receptors, a major family as the direct targets for small-molecule drugs. Li F, Song C, Zhang Y, Wu D. Acta Biochim Biophys Sin (Shanghai) 54 12-24 (2022)
  34. The orphan nuclear receptor estrogen-related receptor beta (ERRβ) in triple-negative breast cancer. Fernandez AI, Geng X, Chaldekas K, Harris B, Duttargi A, Berry VL, Berry DL, Mahajan A, Cavalli LR, Győrffy B, Tan M, Riggins RB. Breast Cancer Res Treat 179 585-604 (2020)
  35. The pERK of being a target: Kinase regulation of the orphan nuclear receptor ERRγ. Riggins RB. Receptors Clin Investig 1 e207 (2014)
  36. Conformational Changes of RORγ During Response Element Recognition and Coregulator Engagement. Strutzenberg TS, Zhu Y, Novick SJ, Garcia-Ordonez RD, Doebelin C, He Y, Chang MR, Kamenecka TM, Edwards DP, Griffin PR. J Mol Biol 433 167258 (2021)
  37. DNA-binding properties of the MADS-domain transcription factor SEPALLATA3 and mutant variants characterized by SELEX-seq. Käppel S, Eggeling R, Rümpler F, Groth M, Melzer R, Theißen G. Plant Mol Biol 105 543-557 (2021)
  38. Estrogen-Related Receptors Gene Expression and Copy Number Alteration Association With the Clinicopathologic Characteristics of Breast Cancer. Shatnawi A, Ayoub NM, Alkhalifa AE, Ibrahim DR. Breast Cancer (Auckl) 16 11782234221086713 (2022)
  39. Innately expressed estrogen-related receptors in the skeletal muscle are indispensable for exercise fitness. Sopariwala DH, Rios AS, Pei G, Roy A, Tomaz da Silva M, Thi Thu Nguyen H, Saley A, Van Drunen R, Kralli A, Mahan K, Zhao Z, Kumar A, Narkar VA. FASEB J 37 e22727 (2023)
  40. The combined action of Esrrb and Nr5a2 is essential for murine naïve pluripotency. Festuccia N, Owens N, Chervova A, Dubois A, Navarro P. Development 148 dev199604 (2021)
  41. Two target gene activation pathways for orphan ERR nuclear receptors. Nakadai T, Shimada M, Ito K, Cevher MA, Chu CS, Kumegawa K, Maruyama R, Malik S, Roeder RG. Cell Res 33 165-183 (2023)


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