Details

Autor(en) / Beteiligte

• Phelan, Caroline A
• Gampe, Jr, Robert T
• Lambert, Millard H
• Parks, Derek J
• Montana, Valerie
• Bynum, Jane
• Broderick, Timothy M
• Hu, Xiao
• Williams, Shawn P
• Nolte, Robert T
• Lazar, Mitchell A

Titel

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

Ist Teil von

• Nature structural & molecular biology, 2010-07, Vol.17 (7), p.808

Ort / Verlag

United States

Erscheinungsjahr

2010

Quelle

MEDLINE

Beschreibungen/Notizen

• 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.