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

[1] Steroid receptor-DNA interactions: toward a quantitative connection between energetics and transcriptional regulation [J].

Bain, David L. ;

Connaghan, Keith D. ;

Maluf, Nasib K. ;

Yang, Qin ;

Miura, Michael T. ;

De Angelis, Rolando W. ;

Degala, Gregory D. ;

Lambert, James R. .

NUCLEIC ACIDS RESEARCH, 2014, 42 (02) :691-700

[2] Glucocorticoid Receptor-DNA Interactions: Binding Energetics Are the Primary Determinant of Sequence-Specific Transcriptional Activity [J].

Bain, David L. ;

Yang, Qin ;

Connaghan, Keith D. ;

Robblee, James P. ;

Miura, Michael T. ;

Degala, Gregory D. ;

Lambert, James R. ;

Maluf, Nasib K. .

JOURNAL OF MOLECULAR BIOLOGY, 2012, 422 (01) :18-32

[3] Low-Resolution Molecular Models Reveal the Oligomeric State of the PPAR and the Conformational Organization of Its Domains in Solution [J].

Bernardes, Amanda ;

Batista, Fernanda A. H. ;

Neto, Mario de Oliveira ;

Figueira, Ana Carolina M. ;

Webb, Paul ;

Saidemberg, Daniel ;

Palma, Mario S. ;

Polikarpov, Igor .

PLOS ONE, 2012, 7 (02)

[4] Improving digestion efficiency under H/D exchange conditions with activated pepsinogen coupled columns [J].

Busby, Scott A. ;

Chalmers, Michael J. ;

Griffin, Patrick R. .

INTERNATIONAL JOURNAL OF MASS SPECTROMETRY, 2007, 259 (1-3) :130-139

[5]

Chalmers Michael J, 2007, J Biomol Tech, V18, P194

[6] Probing protein ligand interactions by automated hydrogen/deuterium exchange mass spectrometry [J].

Chalmers, MJ ;

Busby, SA ;

Pascal, BD ;

He, YJ ;

Hendrickson, CL ;

Marshall, AG ;

Griffin, PR .

ANALYTICAL CHEMISTRY, 2006, 78 (04) :1005-1014

[7] Structure of the intact PPAR-γ-RXR-α nuclear receptor complex on DNA [J].

Chandra, Vikas ;

Huang, Pengxiang ;

Hamuro, Yoshitomo ;

Raghuram, Srilatha ;

Wang, Yongjun ;

Burris, Thomas P. ;

Rastinejad, Fraydoon .

NATURE, 2008, 456 (7220) :350-U33

[8] Multidomain integration in the structure of the HNF-4α nuclear receptor complex [J].

Chandra, Vikas ;

Huang, Pengxiang ;

Potluri, Nalini ;

Wu, Dalei ;

Kim, Youngchang ;

Rastinejad, Fraydoon .

NATURE, 2013, 495 (7441) :394-398

[9]

Chang CY, 1999, MOL CELL BIOL, V19, P8226

[10] Structure and specificity of nuclear receptor-coactivator interactions [J].

Darimont, BD ;

Wagner, RL ;

Apriletti, JW ;

Stallcup, MR ;

Kushner, PJ ;

Baxter, JD ;

Fletterick, RJ ;

Yamamoto, KR .

GENES & DEVELOPMENT, 1998, 12 (21) :3343-3356

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