1ZH7

Structural and Biochemical Basis for Selective Repression of the Orphan Nuclear Receptor LRH-1 by SHP


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.50 Å
  • R-Value Free: 0.285 
  • R-Value Work: 0.226 
  • R-Value Observed: 0.226 

wwPDB Validation   3D Report Full Report


This is version 1.4 of the entry. See complete history


Literature

Structural and biochemical basis for selective repression of the orphan nuclear receptor liver receptor homolog 1 by small heterodimer partner

Li, Y.Choi, M.Suino, K.Kovach, A.Daugherty, J.Kliewer, S.A.Xu, H.E.

(2005) Proc Natl Acad Sci U S A 102: 9505-9510

  • DOI: https://doi.org/10.1073/pnas.0501204102
  • Primary Citation of Related Structures:  
    1ZGY, 1ZH7

  • PubMed Abstract: 

    The functional interaction between the orphan nuclear receptors small heterodimer partner (SHP) and liver receptor homolog 1 (LRH-1), where SHP binds to LRH-1 and represses its constitutive transcriptional activity, is crucial for regulating genes involved in cholesterol homeostasis. Here, we report structural and biochemical analyses of the LRH-1/SHP interaction. The crystal structure and modeling studies of the LRH-1 ligand-binding domain bound to either of the two LXXLL-related motifs of SHP show that the receptor undergoes conformational changes to accommodate the SHP docking and reveal key residues that determine the potency and selectivity of SHP binding. Through a combination of mutagenesis and binding studies, we demonstrate that only the second SHP LXXLL motif is required for repressing LRH-1, and this motif displays a strong preference for binding to LRH-1 over the closely related receptor steroidogeneic factor 1 (SF-1). Structural comparisons indicate that this binding selectivity is determined by residues flanking the core LXXLL motifs. These results establish a structural model for understanding how SHP interacts with LRH-1 to regulate cholesterol homeostasis and provide new insights into how nuclear receptor/coregulator selectivity is achieved.


  • Organizational Affiliation

    Laboratory of Structural Sciences, Van Andel Research Institute, 333 Bostwick Avenue, Grand Rapids, MI 49503, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Orphan nuclear receptor NR5A2
A, B
243Mus musculusMutation(s): 0 
UniProt
Find proteins for P45448 (Mus musculus)
Explore P45448 
Go to UniProtKB:  P45448
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP45448
Sequence Annotations
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  • Reference Sequence

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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
nuclear receptor subfamily 0, group B, member 2
C, D
11Rattus norvegicusMutation(s): 0 
UniProt
Find proteins for P97947 (Rattus norvegicus)
Explore P97947 
Go to UniProtKB:  P97947
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP97947
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.50 Å
  • R-Value Free: 0.285 
  • R-Value Work: 0.226 
  • R-Value Observed: 0.226 
  • Space Group: C 1 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 113.765α = 90
b = 35.126β = 92.61
c = 134.205γ = 90
Software Package:
Software NamePurpose
CNSrefinement
MAR345data collection
SCALEPACKdata scaling
AMoREphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2005-08-02
    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: 2017-10-11
    Changes: Refinement description
  • Version 1.4: 2024-02-14
    Changes: Data collection, Database references