Structural insights into corepressor recognition by antagonist-bound estrogen receptors

Nina Heldring, Tanya Pawson, Donald McDonnell, Eckardt Treuter, Jan Åke Gustafsson, Ashley C.W. Pike

Research output: Contribution to journalArticlepeer-review

64 Scopus citations


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 ERα 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.

Original languageEnglish (US)
Pages (from-to)10449-10455
Number of pages7
JournalJournal of Biological Chemistry
Issue number14
StatePublished - Apr 6 2007

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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