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

Research output: Contribution to journalArticle

1 Citation (Scopus)

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 languageEnglish (US)
Pages (from-to)229-240.e4
JournalStructure
Volume27
Issue number2
DOIs
StatePublished - Feb 5 2019
Externally publishedYes

Fingerprint

Mutagenesis
Estrogen Receptors
Transcriptional Activation
Phosphorylation
Breast Neoplasms

Keywords

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

ASJC Scopus subject areas

  • Structural Biology
  • Molecular Biology

Cite this

Peng, Y., Cao, S., Kiselar, J., Xiao, X., Du, Z., Hsieh, A., ... Yang, S. (2019). A Metastable Contact and Structural Disorder in the Estrogen Receptor Transactivation Domain. Structure, 27(2), 229-240.e4. https://doi.org/10.1016/j.str.2018.10.026

A Metastable Contact and Structural Disorder in the Estrogen Receptor Transactivation Domain. / Peng, Yi; Cao, Shufen; Kiselar, Janna; Xiao, Xiangzhu; Du, Zhanwen; Hsieh, An; Ko, Soobin; Chen, Yinghua; Agrawal, Prashansa; Zheng, Wenwei; Shi, Wuxian; Jiang, Wei; Yang, Lin; Chance, Mark R.; Surewicz, Witold K.; Buck, Matthias; Yang, Sichun.

In: Structure, Vol. 27, No. 2, 05.02.2019, p. 229-240.e4.

Research output: Contribution to journalArticle

Peng, Y, Cao, S, Kiselar, J, Xiao, X, Du, Z, Hsieh, A, Ko, S, Chen, Y, Agrawal, P, Zheng, W, Shi, W, Jiang, W, Yang, L, Chance, MR, Surewicz, WK, Buck, M & Yang, S 2019, 'A Metastable Contact and Structural Disorder in the Estrogen Receptor Transactivation Domain', Structure, vol. 27, no. 2, pp. 229-240.e4. https://doi.org/10.1016/j.str.2018.10.026
Peng, Yi ; Cao, Shufen ; Kiselar, Janna ; Xiao, Xiangzhu ; Du, Zhanwen ; Hsieh, An ; Ko, Soobin ; Chen, Yinghua ; Agrawal, Prashansa ; Zheng, Wenwei ; Shi, Wuxian ; Jiang, Wei ; Yang, Lin ; Chance, Mark R. ; Surewicz, Witold K. ; Buck, Matthias ; Yang, Sichun. / A Metastable Contact and Structural Disorder in the Estrogen Receptor Transactivation Domain. In: Structure. 2019 ; Vol. 27, No. 2. pp. 229-240.e4.
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