A Metastable Contact and Structural Disorder in the Estrogen Receptor Transactivation Domain

Yi Peng; Shufen Cao; Janna Kiselar; Xiangzhu Xiao; Zhanwen Du; An Hsieh; Soobin Ko; Yinghua Chen; Prashansa Agrawal; Wenwei Zheng; Wuxian Shi; Wei Jiang; Lin Yang; Mark R. Chance; Witold K. Surewicz; Matthias Buck; Sichun Yang

doi:10.1016/j.str.2018.10.026

A Metastable Contact and Structural Disorder in the Estrogen Receptor Transactivation Domain

Yi Peng, Shufen Cao, Janna Kiselar, Xiangzhu Xiao, Zhanwen Du, An Hsieh, Soobin Ko, Yinghua Chen, Prashansa Agrawal, Wenwei Zheng, Wuxian Shi, Wei Jiang, Lin Yang, Mark R. Chance, Witold K. Surewicz, Matthias Buck, Sichun Yang

Integrative Sciences and Arts, College of (CISA)

Research output: Contribution to journal › Article › peer-review

33 Scopus citations

Abstract

We unraveled that the transactivation domain of estrogen receptor is structurally disordered, yet unexpectedly compact, and that a metastable Ile33-Ser118 contact is observed to inhibit coactivator binding. Disruption by mutagenesis alters ensemble-structures and coactivator binding, providing a functional link of oncogenic Ser118 phosphorylation in breast cancer endocrine resistance.

Original language	English (US)
Pages (from-to)	229-240.e4
Journal	Structure
Volume	27
Issue number	2
DOIs	https://doi.org/10.1016/j.str.2018.10.026
State	Published - Feb 5 2019

Keywords

SAXS
contact metastability
intrinsically disordered protein
multi-technique data integration
protein footprinting
structural disorder

ASJC Scopus subject areas

Structural Biology
Molecular Biology

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10.1016/j.str.2018.10.026

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title = "A Metastable Contact and Structural Disorder in the Estrogen Receptor Transactivation Domain",

abstract = "We unraveled that the transactivation domain of estrogen receptor is structurally disordered, yet unexpectedly compact, and that a metastable Ile33-Ser118 contact is observed to inhibit coactivator binding. Disruption by mutagenesis alters ensemble-structures and coactivator binding, providing a functional link of oncogenic Ser118 phosphorylation in breast cancer endocrine resistance.",

keywords = "SAXS, contact metastability, intrinsically disordered protein, multi-technique data integration, protein footprinting, structural disorder",

author = "Yi Peng and Shufen Cao and Janna Kiselar and Xiangzhu Xiao and Zhanwen Du and An Hsieh and Soobin Ko and Yinghua Chen and Prashansa Agrawal and Wenwei Zheng and Wuxian Shi and Wei Jiang and Lin Yang and Chance, {Mark R.} and Surewicz, {Witold K.} and Matthias Buck and Sichun Yang",

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doi = "10.1016/j.str.2018.10.026",

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T1 - A Metastable Contact and Structural Disorder in the Estrogen Receptor Transactivation Domain

AU - Peng, Yi

AU - Cao, Shufen

AU - Kiselar, Janna

AU - Xiao, Xiangzhu

AU - Du, Zhanwen

AU - Hsieh, An

AU - Ko, Soobin

AU - Chen, Yinghua

AU - Agrawal, Prashansa

AU - Zheng, Wenwei

AU - Shi, Wuxian

AU - Jiang, Wei

AU - Yang, Lin

AU - Chance, Mark R.

AU - Surewicz, Witold K.

AU - Buck, Matthias

AU - Yang, Sichun

PY - 2019/2/5

Y1 - 2019/2/5

N2 - We unraveled that the transactivation domain of estrogen receptor is structurally disordered, yet unexpectedly compact, and that a metastable Ile33-Ser118 contact is observed to inhibit coactivator binding. Disruption by mutagenesis alters ensemble-structures and coactivator binding, providing a functional link of oncogenic Ser118 phosphorylation in breast cancer endocrine resistance.

AB - We unraveled that the transactivation domain of estrogen receptor is structurally disordered, yet unexpectedly compact, and that a metastable Ile33-Ser118 contact is observed to inhibit coactivator binding. Disruption by mutagenesis alters ensemble-structures and coactivator binding, providing a functional link of oncogenic Ser118 phosphorylation in breast cancer endocrine resistance.

KW - SAXS

KW - contact metastability

KW - intrinsically disordered protein

KW - multi-technique data integration

KW - protein footprinting

KW - structural disorder

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ER -

A Metastable Contact and Structural Disorder in the Estrogen Receptor Transactivation Domain

Abstract

Keywords

ASJC Scopus subject areas

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