DNA allosterically modulates the steroid binding domain of the estrogen receptor

M. Fritsch, R. D. Welch, F. E. Murdoch, I. Anderson, J. Gorski

Research output: Contribution to journalArticle

42 Scopus citations

Abstract

The ability of DNA to allosterically alter the conformation of the estrogen receptor's (ER) steroid binding domain was investigated. Using dissociation kinetics we observed that when DNA was bound to the DNA binding domain of the rat uterine ER the rate of estrogen dissociation from the steroid binding domain increased almost 2-fold. This change in the rate of estrogen dissociation depended on the concentration of DNA used and correlated with the thermodynamic binding affinities (K(d)) of the ER for two different DNA sequences. We were unable to detect a DNA-induced change in the trypsin cleavage pattern of the amino terminal end of the ER. Using a whole cell dissociation kinetics assay with MCF-7 breast cancer cells we observed a 7-fold slower rate of estrogen dissociation from the ER within the cell than from the ER in vitro. This suggests that additional factors, other than DNA binding, may modify the steroid binding domain within the cell. We conclude that DNA can allosterically modulate the structure of the steroid binding domain of the ER, and we hypothesize that this conformational change may be necessary for the full transcriptional activity of the ER.

Original languageEnglish (US)
Pages (from-to)1823-1828
Number of pages6
JournalJournal of Biological Chemistry
Volume267
Issue number3
StatePublished - Jan 1 1992
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Fingerprint Dive into the research topics of 'DNA allosterically modulates the steroid binding domain of the estrogen receptor'. Together they form a unique fingerprint.

  • Cite this

    Fritsch, M., Welch, R. D., Murdoch, F. E., Anderson, I., & Gorski, J. (1992). DNA allosterically modulates the steroid binding domain of the estrogen receptor. Journal of Biological Chemistry, 267(3), 1823-1828.