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Estrogen receptor (ER) modulators each induce distinct conformational changes in ER alpha and ER beta.

Publication ,  Journal Article
Paige, LA; Christensen, DJ; Grøn, H; Norris, JD; Gottlin, EB; Padilla, KM; Chang, CY; Ballas, LM; Hamilton, PT; McDonnell, DP; Fowlkes, DM
Published in: Proc Natl Acad Sci U S A
March 30, 1999

Estrogen receptor (ER) modulators produce distinct tissue-specific biological effects, but within the confines of the established models of ER action it is difficult to understand why. Previous studies have suggested that there might be a relationship between ER structure and activity. Different ER modulators may induce conformational changes in the receptor that result in a specific biological activity. To investigate the possibility of modulator-specific conformational changes, we have applied affinity selection of peptides to identify binding surfaces that are exposed on the apo-ERs alpha and beta and on each receptor complexed with estradiol or 4-OH tamoxifen. These peptides are sensitive probes of receptor conformation. We show here that ER ligands, known to produce distinct biological effects, induce distinct conformational changes in the receptors, providing a strong correlation between ER conformation and biological activity. Furthermore, the ability of some of the peptides to discriminate between different ER alpha and ER beta ligand complexes suggests that the biological effects of ER agonists and antagonists acting through these receptors are likely to be different.

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Published In

Proc Natl Acad Sci U S A

DOI

ISSN

0027-8424

Publication Date

March 30, 1999

Volume

96

Issue

7

Start / End Page

3999 / 4004

Location

United States

Related Subject Headings

  • Tamoxifen
  • Sequence Homology, Amino Acid
  • Sequence Alignment
  • Receptors, Estrogen
  • Protein Conformation
  • Molecular Sequence Data
  • Humans
  • Estrogens
  • Estrogen Receptor beta
  • Estrogen Receptor alpha
 

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Paige, L. A., Christensen, D. J., Grøn, H., Norris, J. D., Gottlin, E. B., Padilla, K. M., … Fowlkes, D. M. (1999). Estrogen receptor (ER) modulators each induce distinct conformational changes in ER alpha and ER beta. Proc Natl Acad Sci U S A, 96(7), 3999–4004. https://doi.org/10.1073/pnas.96.7.3999
Paige, L. A., D. J. Christensen, H. Grøn, J. D. Norris, E. B. Gottlin, K. M. Padilla, C. Y. Chang, et al. “Estrogen receptor (ER) modulators each induce distinct conformational changes in ER alpha and ER beta.Proc Natl Acad Sci U S A 96, no. 7 (March 30, 1999): 3999–4004. https://doi.org/10.1073/pnas.96.7.3999.
Paige LA, Christensen DJ, Grøn H, Norris JD, Gottlin EB, Padilla KM, et al. Estrogen receptor (ER) modulators each induce distinct conformational changes in ER alpha and ER beta. Proc Natl Acad Sci U S A. 1999 Mar 30;96(7):3999–4004.
Paige, L. A., et al. “Estrogen receptor (ER) modulators each induce distinct conformational changes in ER alpha and ER beta.Proc Natl Acad Sci U S A, vol. 96, no. 7, Mar. 1999, pp. 3999–4004. Pubmed, doi:10.1073/pnas.96.7.3999.
Paige LA, Christensen DJ, Grøn H, Norris JD, Gottlin EB, Padilla KM, Chang CY, Ballas LM, Hamilton PT, McDonnell DP, Fowlkes DM. Estrogen receptor (ER) modulators each induce distinct conformational changes in ER alpha and ER beta. Proc Natl Acad Sci U S A. 1999 Mar 30;96(7):3999–4004.
Journal cover image

Published In

Proc Natl Acad Sci U S A

DOI

ISSN

0027-8424

Publication Date

March 30, 1999

Volume

96

Issue

7

Start / End Page

3999 / 4004

Location

United States

Related Subject Headings

  • Tamoxifen
  • Sequence Homology, Amino Acid
  • Sequence Alignment
  • Receptors, Estrogen
  • Protein Conformation
  • Molecular Sequence Data
  • Humans
  • Estrogens
  • Estrogen Receptor beta
  • Estrogen Receptor alpha