PMID- 10835357
OWN - NLM
STAT- MEDLINE
DCOM- 20000720
LR  - 20240314
IS  - 0261-4189 (Print)
IS  - 1460-2075 (Electronic)
IS  - 0261-4189 (Linking)
VI  - 19
IP  - 11
DP  - 2000 Jun 1
TI  - Crystal structure of the human RXRalpha ligand-binding domain bound to its 
      natural ligand: 9-cis retinoic acid.
PG  - 2592-601
AB  - The pleiotropic effects of active retinoids are transduced by their cognate 
      nuclear receptors, retinoid X receptors (RXRs) and retinoic acid receptors 
      (RARs), which act as transcriptional regulators activated by two stereoisomers of 
      retinoic acid (RA): 9-cis RA (9-cRA) and all-trans RA (a-tRA). Among nuclear 
      receptors, RXR occupies a central position and plays a crucial role in many 
      intracellular signalling pathways as a ubiquitous heterodimerization partner with 
      numerous other members of this superfamily. Whereas RARs bind both isomers, RXRs 
      exclusively bind 9-cRA. The crystal structure of the ligand-binding domain (LBD) 
      of human RXRalpha bound to 9-cRA reveals the molecular basis of this ligand 
      selectivity and allows a comparison of both apo and holo forms of the same 
      nuclear receptor. In the crystal, the receptor is monomeric and exhibits a 
      canonical agonist conformation without direct contacts between the ligand and the 
      transactivation helix H12. Comparison with the unliganded RXRalpha LBD structure 
      reveals the molecular mechanisms of ligand-induced conformational changes and 
      allows us to describe at the atomic level how these changes generate the proper 
      protein interface involved in nuclear receptor-coactivator interaction.
FAU - Egea, P F
AU  - Egea PF
AD  - Institut de Genetique et de Biologie Moleculaire et Cellulaire, 
      CNRS/INSERM/ULP/College de France, BP 163-67404 Illkirch Cedex, CU de Strasbourg, 
      France.
FAU - Mitschler, A
AU  - Mitschler A
FAU - Rochel, N
AU  - Rochel N
FAU - Ruff, M
AU  - Ruff M
FAU - Chambon, P
AU  - Chambon P
FAU - Moras, D
AU  - Moras D
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - EMBO J
JT  - The EMBO journal
JID - 8208664
RN  - 0 (Apoproteins)
RN  - 0 (Ligands)
RN  - 0 (Macromolecular Substances)
RN  - 0 (Peptide Fragments)
RN  - 0 (Receptors, Retinoic Acid)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Retinoid X Receptors)
RN  - 0 (Transcription Factors)
RN  - 1UA8E65KDZ (Alitretinoin)
RN  - 5688UTC01R (Tretinoin)
SB  - IM
MH  - Alitretinoin
MH  - Apoproteins/chemistry/metabolism
MH  - Binding Sites
MH  - Crystallization
MH  - Crystallography, X-Ray
MH  - Humans
MH  - Ligands
MH  - Macromolecular Substances
MH  - Models, Molecular
MH  - Peptide Fragments/chemistry/metabolism
MH  - Protein Binding
MH  - Protein Conformation
MH  - Receptors, Retinoic Acid/*chemistry/genetics/metabolism
MH  - Recombinant Fusion Proteins/chemistry/metabolism
MH  - Retinoid X Receptors
MH  - Stereoisomerism
MH  - Transcription Factors/*chemistry/genetics/metabolism
MH  - Transcriptional Activation
MH  - Tretinoin/*metabolism
PMC - PMC212755
EDAT- 2000/06/03 09:00
MHDA- 2000/07/25 11:00
PMCR- 2001/06/01
CRDT- 2000/06/03 09:00
PHST- 2000/06/03 09:00 [pubmed]
PHST- 2000/07/25 11:00 [medline]
PHST- 2000/06/03 09:00 [entrez]
PHST- 2001/06/01 00:00 [pmc-release]
AID - cdd254 [pii]
AID - 10.1093/emboj/19.11.2592 [doi]
PST - ppublish
SO  - EMBO J. 2000 Jun 1;19(11):2592-601. doi: 10.1093/emboj/19.11.2592.