Structure of Rev-erbalpha bound to N-CoR reveals a unique mechanism of nuclear receptor-co-repressor interaction

Nat Struct Mol Biol. 2010 Jul;17(7):808-14. doi: 10.1038/nsmb.1860. Epub 2010 Jun 27.

Abstract

Repression of gene transcription by the nuclear receptor Rev-erbalpha plays an integral role in the core molecular circadian clock. We report the crystal structure of a nuclear receptor-co-repressor (N-CoR) interaction domain 1 (ID1) peptide bound to truncated human Rev-erbalpha ligand-binding domain (LBD). The ID1 peptide forms an unprecedented antiparallel beta-sheet with Rev-erbalpha, as well as an alpha-helix similar to that seen in nuclear receptor ID2 crystal structures but out of register by four residues. Comparison with the structure of Rev-erbbeta bound to heme indicates that ID1 peptide and heme induce substantially different conformational changes in the LBD. Although heme is involved in Rev-erb repression, the structure suggests that Rev-erbalpha could also mediate repression via ID1 binding in the absence of heme. The previously uncharacterized secondary structure induced by ID1 peptide binding advances our understanding of nuclear receptor-co-repressor interactions.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Cell Line
  • Crystallography, X-Ray
  • Humans
  • Ligands
  • Models, Molecular
  • Molecular Sequence Data
  • Nuclear Receptor Co-Repressor 1 / chemistry
  • Nuclear Receptor Co-Repressor 1 / metabolism*
  • Nuclear Receptor Subfamily 1, Group D, Member 1 / chemistry*
  • Nuclear Receptor Subfamily 1, Group D, Member 1 / metabolism*
  • Protein Binding
  • Protein Structure, Secondary
  • Protein Structure, Tertiary
  • Sequence Alignment

Substances

  • Ligands
  • NR1D1 protein, human
  • Nuclear Receptor Co-Repressor 1
  • Nuclear Receptor Subfamily 1, Group D, Member 1

Associated data

  • PDB/3N00