A Ligand-Induced Conformational Change in the Estrogen Receptor Is Localized in the Steroid Binding Domain

Michael Fritsch, Cynthia M. Leary, John Furlow, Jack Gorski, Helga Ahrens, Gerald C. Mueller, Timothy J. Schuh

Research output: Contribution to journalArticle

52 Citations (Scopus)

Abstract

Upon binding estrogen, the estrogen receptor (ER) is proposed to undergo some form of conformational transition leading to increased transcription from estrogen-responsive genes. In vitro methods used to study the transition often do not separate heat-induced effects on the ER from estrogen-induced effects. The technique of affinity partitioning with PEG-palmitate was used to study the change in the hydrophobic surface properties of the ER upon binding ligand with and without in vitro heating. Upon binding estradiol (E2), the full-length rat uterine cytosolic ER undergoes a dramatic decrease in surface hydrophobicity. The binding of the anti-estrogen 4-hydroxytamoxifen (4-OHT) results in a similar decrease in surface hydrophobicity. These effects are independent of any conformational changes induced by heating the ER to 30 °C for 45 min. The use of the human ER steroid binding domain overproduced in Escherichia coli (ER-C) and the trypsin-generated steroid binding domain from rat uterine cytosolic ER demonstrates that the decrease in surface hydrophobicity upon binding E2 or 4-OHT is localized to the steroid binding domain. Gel filtration analysis indicates that the change in surface hydrophobicity upon binding ligand is an inherent property of the steroid binding domain and not due to a ligand-induced change in the oligomeric state of the receptor. The decrease in surface hydrophobicity of the steroid binding domain of the ER upon binding E2 or 4-OHT represents an early and possibly a necessary event in estrogen action and may be important for “tight” binding of the ER in the nucleus.

Original languageEnglish (US)
Pages (from-to)5303-5311
Number of pages9
JournalBiochemistry
Volume31
Issue number23
DOIs
StatePublished - Feb 1 1992
Externally publishedYes

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Estrogen Receptors
Steroids
Ligands
Hydrophobicity
Hydrophobic and Hydrophilic Interactions
Estrogens
Heating
Rats
Surface Properties
Transcription
Trypsin
Escherichia coli
Surface properties
Gel Chromatography
Estradiol
Hot Temperature
Genes
Gels
4,17 beta-dihydroxy-4-androstene-3-one

ASJC Scopus subject areas

  • Biochemistry

Cite this

Fritsch, M., Leary, C. M., Furlow, J., Gorski, J., Ahrens, H., Mueller, G. C., & Schuh, T. J. (1992). A Ligand-Induced Conformational Change in the Estrogen Receptor Is Localized in the Steroid Binding Domain. Biochemistry, 31(23), 5303-5311. https://doi.org/10.1021/bi00138a009

A Ligand-Induced Conformational Change in the Estrogen Receptor Is Localized in the Steroid Binding Domain. / Fritsch, Michael; Leary, Cynthia M.; Furlow, John; Gorski, Jack; Ahrens, Helga; Mueller, Gerald C.; Schuh, Timothy J.

In: Biochemistry, Vol. 31, No. 23, 01.02.1992, p. 5303-5311.

Research output: Contribution to journalArticle

Fritsch, M, Leary, CM, Furlow, J, Gorski, J, Ahrens, H, Mueller, GC & Schuh, TJ 1992, 'A Ligand-Induced Conformational Change in the Estrogen Receptor Is Localized in the Steroid Binding Domain', Biochemistry, vol. 31, no. 23, pp. 5303-5311. https://doi.org/10.1021/bi00138a009
Fritsch, Michael ; Leary, Cynthia M. ; Furlow, John ; Gorski, Jack ; Ahrens, Helga ; Mueller, Gerald C. ; Schuh, Timothy J. / A Ligand-Induced Conformational Change in the Estrogen Receptor Is Localized in the Steroid Binding Domain. In: Biochemistry. 1992 ; Vol. 31, No. 23. pp. 5303-5311.
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