Synergistic Regulation of Coregulator/Nuclear Receptor Interaction by Ligand and DNA

被引：43

作者：

de Vera, Ian Mitchelle S. ^{[1
,2
,4
]}

Zheng, Jie ^{[2
]}

Novick, Scott ^{[2
]}

Shang, Jinsai ^{[1
,2
]}

Hughes, Travis S. ^{[1
,2
,5
]}

Brust, Richard ^{[1
,2
]}

Munoz-Tello, Paola ^{[1
,2
]}

Gardner, William J., Jr. ^{[1
,2
,3
]}

Marciano, David P. ^{[2
]}

Kong, Xiangming ^{[1
,2
]}

Griffin, Patrick R. ^{[2
]}

Kojetin, Douglas J. ^{[1
,2
]}

机构：

[1] Scripps Florida, Scripps Res Inst, Dept Integrat Struct & Computat Biol, Jupiter, FL 33458 USA

[2] Scripps Florida, Scripps Res Inst, Dept Mol Med, Jupiter, FL 33458 USA

[3] Scripps Florida, Scripps Res Inst, TSRI High Sch Student Summer Internship Program, Jupiter, FL 33458 USA

[4] St Louis Univ, Sch Med, Dept Physiol & Pharmacol, St Louis, MO 63104 USA

[5] Univ Montana, Dept Biomed & Pharmaceut Sci, Missoula, MT 59812 USA

来源：

STRUCTURE | 2017年 / 25卷 / 10期

关键词：

RETINOID-X-RECEPTOR; PPAR-GAMMA-RXR; BINDING; EXCHANGE; ALPHA; COMPLEX; ENERGETICS; MECHANISM; DYNAMICS; PEPTIDE;

D O I：

10.1016/j.str.2017.07.019

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Nuclear receptor (NR) transcription factors bind various coreceptors, small-molecule ligands, DNA response element sequences, and transcriptional coregulator proteins to affect gene transcription. Small-molecule ligands and DNA are known to influence receptor structure, coregulator protein interaction, and function; however, little is known on the mechanism of synergy between ligand and DNA. Using quantitative biochemical, biophysical, and solution structural methods, including 13 C-detected nuclearmagnetic resonance and hydrogen/deuterium exchange (HDX) mass spectrometry, we show that ligand and DNA cooperatively recruit the intrinsically disordered steroid receptor coactivator-2 (SRC-2/TIF2/GRIP1/NCoA-2) receptor interaction domain to peroxisome proliferator-activated receptor gammaretinoid X receptor alpha (PPARg-RXRa) heterodimer and reveal the binding determinants of the complex. Our data reveal a thermodynamic mechanism by which DNA binding propagates a conformational change in PPARg-RXRa, stabilizes the receptor ligand binding domain dimer interface, and impacts ligand potency and cooperativity in NR coactivator recruitment.

引用

页码：1506 / +

页数：17

共 54 条

[41] Understanding nuclear receptor form and function using structural biology [J].

Rastinejad, Fraydoon ;

Huang, Pengxiang ;

Chandra, Vikas ;

Khorasanizadeh, Sepideh .

JOURNAL OF MOLECULAR ENDOCRINOLOGY, 2013, 51 (03) :T1-T21

[42] Multiple Binding Modes between HNF4α and the LXXLL Motifs of PGC-1α Lead to Full Activation [J].

Rha, Geun Bae ;

Wu, Guangteng ;

Shoelson, Steven E. ;

Chi, Young-In .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2009, 284 (50) :35165-35176

[43] Common architecture of nuclear receptor heterodimers on DNA direct repeat elements with different spacings [J].

Rochel, Natacha ;

Ciesielski, Fabrice ;

Godet, Julien ;

Moman, Edelmiro ;

Roessle, Manfred ;

Peluso-Iltis, Carole ;

Moulin, Martine ;

Haertlein, Michael ;

Callow, Phil ;

Mely, Yves ;

Svergun, Dmitri I. ;

Moras, Dino .

NATURE STRUCTURAL & MOLECULAR BIOLOGY, 2011, 18 (05) :564-U207

[44] Sequences flanking the core-binding site modulate glucocorticoid receptor structure and activity [J].

Schoene, Stefanie ;

Jurk, Marcel ;

Helabad, Mahdi Bagherpoor ;

Dror, Iris ;

Lebars, Isabelle ;

Kieffer, Bruno ;

Imhof, Petra ;

Rohs, Remo ;

Vingron, Martin ;

Thomas-Chollier, Morgane ;

Meijsing, Sebastiaan H. .

NATURE COMMUNICATIONS, 2016, 7

[45] Selective modulation of promoter recruitment and transcriptional activity of PPARγ [J].

Sears, Dorothy D. ;

Hsiao, Albert ;

Ofrecio, Jachelle M. ;

Chapman, Justin ;

He, Weimin ;

Olefsky, Jerrold M. .

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2007, 364 (03) :515-521

[46] The Asymmetric Binding of PGC-1α to the ERRα and ERRγ Nuclear Receptor Homodimers Involves a Similar Recognition Mechanism [J].

Takacs, Maria ;

Petoukhov, Maxim V. ;

Atkinson, R. Andrew ;

Roblin, Pierre ;

Ogi, Francois-Xavier ;

Demeler, Borries ;

Potier, Noelle ;

Chebaro, Yassmine ;

Dejaegere, Annick ;

Svergun, Dmitri I. ;

Moras, Dino ;

Billas, Isabelle M. L. .

PLOS ONE, 2013, 8 (07)

[47] The glucocorticoid receptor dimer interface allosterically transmits sequence-specific DNA signals [J].

Watson, Lisa C. ;

Kuchenbecker, Kristopher M. ;

Schiller, Benjamin J. ;

Gross, John D. ;

Pufall, Miles A. ;

Yamamoto, Keith R. .

NATURE STRUCTURAL & MOLECULAR BIOLOGY, 2013, 20 (07) :876-+

[48] Thermodynamic characterization of the interaction between CAR-RXR and SRC-1 peptide by isothermal titration calorimetry [J].

Wright, Edward ;

Vincent, Jeremy ;

Fernandez, Elias J. .

BIOCHEMISTRY, 2007, 46 (03) :862-870

[49] Structure, Energetics, and Dynamics of Binding Coactivator Peptide to the Human Retinoid X Receptor α Ligand Binding Domain Complex with 9-cis-Retinoic Acid [J].

Xia, Gang ;

Boerma, LeeAnn J. ;

Cox, Bryan D. ;

Qiu, Cheng ;

Kang, Sebyung ;

Smith, Craig D. ;

Renfrow, Matthew B. ;

Muccio, Donald D. .

BIOCHEMISTRY, 2011, 50 (01) :93-105

[50] Normal and cancer-related functions of the p160 steroid receptor co-activator (SRC) family [J].

Xu, Jianming ;

Wu, Ray-Chang ;

O'Malley, Bert W. .

NATURE REVIEWS CANCER, 2009, 9 (09) :615-630

← 1 2 3 4 5 6 →