Influence of Domain Interactions on Conformational Mobility of the Progesterone Receptor Detected by Hydrogen/Deuterium Exchange Mass Spectrometry

被引：22

作者：

Goswami, Devrishi ^{[1
]}

Callaway, Celetta ^{[3
,4
]}

Pascal, Bruce D. ^{[1
]}

Kumar, Raj ^{[2
]}

Edwards, Dean P. ^{[3
,4
]}

Griffin, Patrick R. ^{[1
]}

机构：

[1] Scripps Res Inst, Dept Mol Therapeut, Jupiter, FL 33458 USA

[2] Commonwealth Med Coll, Dept Basic Sci, Scranton, PA 18510 USA

[3] Baylor Coll Med, Dept Mol & Cellular Biol, Houston, TX 77030 USA

[4] Baylor Coll Med, Dept Pathol & Immunol, Houston, TX 77030 USA

来源：

STRUCTURE | 2014年 / 22卷 / 07期

关键词：

PROTEIN-LIGAND INTERACTIONS; STEROID-HORMONE RECEPTORS; N-TERMINAL REGION; GLUCOCORTICOID-RECEPTOR; ESTROGEN-RECEPTOR; NUCLEAR RECEPTOR; STRUCTURAL BASIS; BREAST-CANCER; IN-VITRO; TRANSCRIPTION FACTORS;

D O I：

10.1016/j.str.2014.04.013

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：

Structural and functional details of the N-terminal activation function 1 (AF1) of most nuclear receptors are poorly understood due to the highly dynamic intrinsically disordered nature of this domain. A hydrogen/deuterium exchange (HDX) mass-spectrometry- based investigation of TATA box-binding protein (TBP) interaction with various domains of progesterone receptor (PR) demonstrate that agonist-bound PR interaction with TBP via AF1 impacts the mobility of the C-terminal AF2. Results from HDX and other biophysical studies involving agonist-and antagonist-bound full-length PR and isolated PR domains reveal the molecular mechanism underlying synergistic transcriptional activation mediated by AF1 and AF2, dominance of PR-B isoform over PR-A, and the necessity of AF2 for full AF1-mediated transcriptional activity. These results provide a comprehensive picture elaborating the underlying mechanism of PR-TBP interactions as a model for studying nuclear receptor (NR)-transcription factor functional interactions.

引用

页码：961 / 973

页数：13

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