1XV9

crystal structure of CAR/RXR heterodimer bound with SRC1 peptide, fatty acid, and 5b-pregnane-3,20-dione.


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.70 Å
  • R-Value Free: 0.239 
  • R-Value Work: 0.181 
  • R-Value Observed: 0.181 

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This is version 1.4 of the entry. See complete history


Literature

A Structural Basis for Constitutive Activity in the Human CAR/RXRalpha Heterodimer.

Xu, R.X.Lambert, M.H.Wisely, B.B.Warren, E.N.Weinert, E.E.Waitt, G.M.Williams, J.D.Collins, J.L.Moore, L.B.Willson, T.M.Moore, J.T.

(2004) Mol Cell 16: 919-928

  • DOI: https://doi.org/10.1016/j.molcel.2004.11.042
  • Primary Citation of Related Structures:  
    1XV9, 1XVP

  • PubMed Abstract: 

    The X-ray crystal structure of the human constitutive androstane receptor (CAR, NR1I3)/retinoid X receptor alpha (RXRalpha, NR2B1) heterodimer sheds light on the mechanism of ligand-independent activation of transcription by nuclear receptors. CAR contains a single-turn Helix X that restricts the conformational freedom of the C-terminal AF2 helix, favoring the active state of the receptor. Helix X and AF2 sit atop four amino acids that shield the CAR ligand binding pocket. A fatty acid ligand was identified in the RXRalpha binding pocket. The endogenous RXRalpha ligand, combined with stabilizing interactions from the heterodimer interface, served to hold RXRalpha in an active conformation. The structure suggests that upon translocation, CAR/RXRalpha heterodimers are preorganized in an active conformation in cells such that they can regulate transcription of target genes. Insights into the molecular basis of CAR constitutive activity can be exploited in the design of inverse agonists as drugs for treatment of obesity.


  • Organizational Affiliation

    Discovery Research, GlaxoSmithKline, Research Triangle Park, NC 27709, USA. robert.x.xu@gsk.com


Macromolecules
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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Retinoic acid receptor RXR-alpha
A, C
236Homo sapiensMutation(s): 0 
Gene Names: RXRANR2B1
UniProt & NIH Common Fund Data Resources
Find proteins for P19793 (Homo sapiens)
Explore P19793 
Go to UniProtKB:  P19793
PHAROS:  P19793
GTEx:  ENSG00000186350 
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UniProt GroupP19793
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  • Reference Sequence
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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Orphan nuclear receptor NR1I3
B, D
246Homo sapiensMutation(s): 0 
UniProt & NIH Common Fund Data Resources
Find proteins for Q14994 (Homo sapiens)
Explore Q14994 
Go to UniProtKB:  Q14994
PHAROS:  Q14994
GTEx:  ENSG00000143257 
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UniProt GroupQ14994
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  • Reference Sequence

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Entity ID: 3
MoleculeChains Sequence LengthOrganismDetailsImage
nuclear receptor coactivator 1 isoform 1
E, F, G, H
13Homo sapiensMutation(s): 0 
UniProt & NIH Common Fund Data Resources
Find proteins for Q15788 (Homo sapiens)
Explore Q15788 
Go to UniProtKB:  Q15788
PHAROS:  Q15788
GTEx:  ENSG00000084676 
Entity Groups  
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UniProt GroupQ15788
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.70 Å
  • R-Value Free: 0.239 
  • R-Value Work: 0.181 
  • R-Value Observed: 0.181 
  • Space Group: P 32 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 128.442α = 90
b = 128.442β = 90
c = 214.53γ = 120
Software Package:
Software NamePurpose
HKL-2000data collection
SCALEPACKdata scaling
AMoREphasing
CNSrefinement
HKL-2000data reduction

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2004-12-28
    Type: Initial release
  • Version 1.1: 2008-04-30
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2016-11-30
    Changes: Other, Source and taxonomy
  • Version 1.4: 2024-02-14
    Changes: Data collection, Database references, Derived calculations