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Structural insights into corepressor recognition by antagonist-bound estrogen receptors.

Publication ,  Journal Article
Heldring, N; Pawson, T; McDonnell, D; Treuter, E; Gustafsson, J-A; Pike, ACW
Published in: J Biol Chem
April 6, 2007

Direct recruitment of transcriptional corepressors to estrogen receptors (ER) is thought to contribute to the tissue-specific effects of clinically important ER antagonists. Here, we present the crystal structures of two affinity-selected peptides in complex with antagonist-bound ERalpha ligand-binding domain. Both peptides adopt helical conformations, bind along the activation function 2 coregulator interaction surface, and mimic corepressor (CoRNR) sequence motif binding. Peptide binding is weak in a wild-type context but significantly enhanced by removal of ER helix 12. This region contains a previously unrecognized CoRNR motif that is able to compete with corepressors for binding to activation function 2, thereby providing a structural explanation for the poor ability of ER to directly interact with classical corepressors. Furthermore, the ability of other sequence motifs to mimic corepressor binding raises the possibility that coregulators do not necessarily require CoRNR motifs for direct recruitment to antagonist-bound ER.

Duke Scholars

Published In

J Biol Chem

DOI

ISSN

0021-9258

Publication Date

April 6, 2007

Volume

282

Issue

14

Start / End Page

10449 / 10455

Location

United States

Related Subject Headings

  • Protein Structure, Quaternary
  • Peptides
  • Models, Molecular
  • Humans
  • Estrogen Receptor beta
  • Estrogen Receptor alpha
  • Biochemistry & Molecular Biology
  • Amino Acid Motifs
  • 34 Chemical sciences
  • 32 Biomedical and clinical sciences
 

Citation

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Heldring, N., Pawson, T., McDonnell, D., Treuter, E., Gustafsson, J.-A., & Pike, A. C. W. (2007). Structural insights into corepressor recognition by antagonist-bound estrogen receptors. J Biol Chem, 282(14), 10449–10455. https://doi.org/10.1074/jbc.M611424200
Heldring, Nina, Tanya Pawson, Donald McDonnell, Eckardt Treuter, Jan-Ake Gustafsson, and Ashley C. W. Pike. “Structural insights into corepressor recognition by antagonist-bound estrogen receptors.J Biol Chem 282, no. 14 (April 6, 2007): 10449–55. https://doi.org/10.1074/jbc.M611424200.
Heldring N, Pawson T, McDonnell D, Treuter E, Gustafsson J-A, Pike ACW. Structural insights into corepressor recognition by antagonist-bound estrogen receptors. J Biol Chem. 2007 Apr 6;282(14):10449–55.
Heldring, Nina, et al. “Structural insights into corepressor recognition by antagonist-bound estrogen receptors.J Biol Chem, vol. 282, no. 14, Apr. 2007, pp. 10449–55. Pubmed, doi:10.1074/jbc.M611424200.
Heldring N, Pawson T, McDonnell D, Treuter E, Gustafsson J-A, Pike ACW. Structural insights into corepressor recognition by antagonist-bound estrogen receptors. J Biol Chem. 2007 Apr 6;282(14):10449–10455.

Published In

J Biol Chem

DOI

ISSN

0021-9258

Publication Date

April 6, 2007

Volume

282

Issue

14

Start / End Page

10449 / 10455

Location

United States

Related Subject Headings

  • Protein Structure, Quaternary
  • Peptides
  • Models, Molecular
  • Humans
  • Estrogen Receptor beta
  • Estrogen Receptor alpha
  • Biochemistry & Molecular Biology
  • Amino Acid Motifs
  • 34 Chemical sciences
  • 32 Biomedical and clinical sciences