1UHL

Crystal structure of the LXRalfa-RXRbeta LBD heterodimer


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.90 Å
  • R-Value Free: 0.326 
  • R-Value Work: 0.219 
  • R-Value Observed: 0.224 

wwPDB Validation   3D Report Full Report


This is version 1.4 of the entry. See complete history


Literature

Crystal structure of the heterodimeric complex of LXRalpha and RXRbeta ligand-binding domains in a fully agonistic conformation

Svensson, S.Ostberg, T.Jacobsson, M.Norstrom, C.Stefansson, K.Hallen, D.Johansson, I.C.Zachrisson, K.Ogg, D.Jendeberg, L.

(2003) EMBO J 22: 4625-4633

  • DOI: https://doi.org/10.1093/emboj/cdg456
  • Primary Citation of Related Structures:  
    1UHL

  • PubMed Abstract: 

    The nuclear receptor heterodimers of liver X receptor (LXR) and retinoid X receptor (RXR) are key transcriptional regulators of genes involved in lipid homeostasis and inflammation. We report the crystal structure of the ligand-binding domains (LBDs) of LXRalpha and RXRbeta complexed to the synthetic LXR agonist T-0901317 and the RXR agonist methoprene acid (Protein Data Base entry 1UHL). Both LBDs are in agonist conformation with GRIP-1 peptides bound at the coactivator binding sites. T-0901317 occupies the center of the LXR ligand-binding pocket and its hydroxyl head group interacts with H421 and W443, residues identified by mutational analysis as critical for ligand-induced transcriptional activation by T-0901317 and various endogenous oxysterols. The topography of the pocket suggests a common anchoring of these oxysterols via their 22-, 24- or 27-hydroxyl group to H421 and W443. Polyunsaturated fatty acids act as LXR antagonists and an E267A mutation was found to enhance their transcriptional inhibition. The present structure provides a powerful tool for the design of novel modulators that can be used to characterize further the physiological functions of the LXR-RXR heterodimer.


  • Organizational Affiliation

    Department of Structural Chemistry, Biovitrum AB, Lindhagensgatan 133, SE-112 76 Stockholm, Sweden. stefan.j.svensson@biovitrum.com


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Retinoic acid receptor RXR-beta236Homo sapiensMutation(s): 0 
UniProt & NIH Common Fund Data Resources
Find proteins for P28702 (Homo sapiens)
Explore P28702 
Go to UniProtKB:  P28702
PHAROS:  P28702
GTEx:  ENSG00000204231 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP28702
Sequence Annotations
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  • Reference Sequence
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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Oxysterols receptor LXR-alpha242Homo sapiensMutation(s): 0 
UniProt & NIH Common Fund Data Resources
Find proteins for Q13133 (Homo sapiens)
Explore Q13133 
Go to UniProtKB:  Q13133
PHAROS:  Q13133
GTEx:  ENSG00000025434 
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UniProt GroupQ13133
Sequence Annotations
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  • Reference Sequence

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Entity ID: 3
MoleculeChains Sequence LengthOrganismDetailsImage
10-mer peptide from Nuclear receptor coactivator 2
C, D
10N/AMutation(s): 0 
UniProt & NIH Common Fund Data Resources
Find proteins for Q15596 (Homo sapiens)
Explore Q15596 
Go to UniProtKB:  Q15596
PHAROS:  Q15596
GTEx:  ENSG00000140396 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ15596
Sequence Annotations
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  • Reference Sequence
Small Molecules
Ligands 2 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
444
Query on 444

Download Ideal Coordinates CCD File 
F [auth B]N-(2,2,2-TRIFLUOROETHYL)-N-{4-[2,2,2-TRIFLUORO-1-HYDROXY-1-(TRIFLUOROMETHYL)ETHYL]PHENYL}BENZENESULFONAMIDE
C17 H12 F9 N O3 S
SGIWFELWJPNFDH-UHFFFAOYSA-N
MEI
Query on MEI

Download Ideal Coordinates CCD File 
E [auth A](2E,4E)-11-METHOXY-3,7,11-TRIMETHYLDODECA-2,4-DIENOIC ACID
C16 H28 O3
MNYBEULOKRVZKY-ATCPXPEISA-N
Binding Affinity Annotations 
IDSourceBinding Affinity
444 BindingDB:  1UHL Ki: 24 (nM) from 1 assay(s)
Kd: 92 (nM) from 1 assay(s)
IC50: min: 9, max: 2.60e+4 (nM) from 9 assay(s)
EC50: min: 3.2, max: 1430 (nM) from 30 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.90 Å
  • R-Value Free: 0.326 
  • R-Value Work: 0.219 
  • R-Value Observed: 0.224 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 67.634α = 90
b = 88.996β = 90
c = 90.795γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
DENZOdata reduction
SCALEPACKdata scaling
MOLREPphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2004-06-01
    Type: Initial release
  • Version 1.1: 2008-04-27
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2018-05-23
    Changes: Data collection
  • Version 1.4: 2023-10-25
    Changes: Data collection, Database references, Derived calculations, Refinement description