PMID- 12958591
OWN - NLM
STAT- MEDLINE
DCOM- 20031202
LR  - 20131121
IS  - 1072-8368 (Print)
IS  - 1072-8368 (Linking)
VI  - 10
IP  - 10
DP  - 2003 Oct
TI  - All-trans retinoic acid is a ligand for the orphan nuclear receptor ROR beta.
PG  - 820-5
AB  - Retinoids regulate gene expression through binding to the nuclear retinoic acid 
      receptors (RARs) and retinoid X receptors (RXRs). In contrast, no ligands for the 
      retinoic acid receptor-related orphan receptors beta and gamma (ROR beta and 
      gamma) have been identified, yet structural data and structure-function analyses 
      indicate that ROR beta is a ligand-regulated nuclear receptor. Using 
      nondenaturing mass spectrometry and scintillation proximity assays we found that 
      all-trans retinoic acid (ATRA) and several retinoids bind to the ROR beta 
      ligand-binding domain (LBD). The crystal structures of the complex with ATRA and 
      with the synthetic analog ALRT 1550 reveal the binding modes of these ligands. 
      ATRA and related retinoids inhibit ROR beta but not ROR alpha transcriptional 
      activity suggesting that high-affinity, subtype-specific ligands could be 
      designed for the identification of ROR beta target genes. Our results identify 
      ROR beta as a retinoid-regulated nuclear receptor, providing a novel pathway for 
      retinoid action.
FAU - Stehlin-Gaon, Catherine
AU  - Stehlin-Gaon C
AD  - Departement de Biologie et Genomique Structurales, Institut de Genetique et de 
      Biologie Moleculaire et Cellulaire, 1 rue Laurent Fries, 67404 Illkirch, France.
FAU - Willmann, Dominica
AU  - Willmann D
FAU - Zeyer, Denis
AU  - Zeyer D
FAU - Sanglier, Sarah
AU  - Sanglier S
FAU - Van Dorsselaer, Alain
AU  - Van Dorsselaer A
FAU - Renaud, Jean-Paul
AU  - Renaud JP
FAU - Moras, Dino
AU  - Moras D
FAU - Schule, Roland
AU  - Schule R
LA  - eng
SI  - PDB/1N4H
SI  - PDB/1NQ7
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20030907
PL  - United States
TA  - Nat Struct Biol
JT  - Nature structural biology
JID - 9421566
RN  - 0 (Ligands)
RN  - 0 (Nuclear Receptor Subfamily 1, Group F, Member 2)
RN  - 0 (Receptors, Cytoplasmic and Nuclear)
RN  - 5688UTC01R (Tretinoin)
SB  - IM
MH  - Crystallography, X-Ray
MH  - Humans
MH  - Ligands
MH  - Nuclear Receptor Subfamily 1, Group F, Member 2
MH  - Receptors, Cytoplasmic and Nuclear/*metabolism
MH  - Tretinoin/*metabolism
EDAT- 2003/09/06 05:00
MHDA- 2003/12/03 05:00
CRDT- 2003/09/06 05:00
PHST- 2002/10/28 00:00 [received]
PHST- 2003/07/31 00:00 [accepted]
PHST- 2003/09/06 05:00 [pubmed]
PHST- 2003/12/03 05:00 [medline]
PHST- 2003/09/06 05:00 [entrez]
AID - nsb979 [pii]
AID - 10.1038/nsb979 [doi]
PST - ppublish
SO  - Nat Struct Biol. 2003 Oct;10(10):820-5. doi: 10.1038/nsb979. Epub 2003 Sep 7.