4XAJ

Crystal structure of human NR2E1/TLX


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.55 Å
  • R-Value Free: 0.314 
  • R-Value Work: 0.273 
  • R-Value Observed: 0.275 

wwPDB Validation   3D Report Full Report


This is version 2.1 of the entry. See complete history


Literature

Structural basis for corepressor assembly by the orphan nuclear receptor TLX.

Zhi, X.Zhou, X.E.He, Y.Searose-Xu, K.Zhang, C.L.Tsai, C.C.Melcher, K.Xu, H.E.

(2015) Genes Dev 29: 440-450

  • DOI: https://doi.org/10.1101/gad.254904.114
  • Primary Citation of Related Structures:  
    4XAI, 4XAJ

  • PubMed Abstract: 

    The orphan nuclear receptor TLX regulates neural stem cell self-renewal in the adult brain and functions primarily as a transcription repressor through recruitment of Atrophin corepressors, which bind to TLX via a conserved peptide motif termed the Atro box. Here we report crystal structures of the human and insect TLX ligand-binding domain in complex with Atro box peptides. In these structures, TLX adopts an autorepressed conformation in which its helix H12 occupies the coactivator-binding groove. Unexpectedly, H12 in this autorepressed conformation forms a novel binding pocket with residues from helix H3 that accommodates a short helix formed by the conserved ALXXLXXY motif of the Atro box. Mutations that weaken the TLX-Atrophin interaction compromise the repressive activity of TLX, demonstrating that this interaction is required for Atrophin to confer repressor activity to TLX. Moreover, the autorepressed conformation is conserved in the repressor class of orphan nuclear receptors, and mutations of corresponding residues in other members of this class of receptors diminish their repressor activities. Together, our results establish the functional conservation of the autorepressed conformation and define a key sequence motif in the Atro box that is essential for TLX-mediated repression.


  • Organizational Affiliation

    Laboratory of Structural Sciences, Van Andel Research Institute, Grand Rapids, Michigan 49503, USA; Autophagy Research Center, eric.xu@vai.org xiaoyong.zhi@utsouthwestern.edu.


Macromolecules
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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Maltose-binding periplasmic protein,Nuclear receptor subfamily 2 group E member 1A,
B [auth C],
D [auth B],
E [auth D]
576Escherichia coli O157:H7Homo sapiens
This entity is chimeric
Mutation(s): 4 
Gene Names: malEZ5632ECs5017NR2E1TLX
UniProt & NIH Common Fund Data Resources
Find proteins for P0AEX9 (Escherichia coli (strain K12))
Explore P0AEX9 
Go to UniProtKB:  P0AEX9
Find proteins for Q9Y466 (Homo sapiens)
Explore Q9Y466 
Go to UniProtKB:  Q9Y466
PHAROS:  Q9Y466
GTEx:  ENSG00000112333 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupsQ9Y466P0AEX9
Sequence Annotations
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  • Reference Sequence

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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Atrophin/grungeC [auth Q],
F [auth P]
18Drosophila melanogasterMutation(s): 0 
UniProt
Find proteins for M9PHT1 (Drosophila melanogaster)
Explore M9PHT1 
Go to UniProtKB:  M9PHT1
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupM9PHT1
Sequence Annotations
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  • Reference Sequence
Oligosaccharides

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Entity ID: 3
MoleculeChains Length2D Diagram Glycosylation3D Interactions
alpha-D-glucopyranose-(1-4)-alpha-D-glucopyranoseG [auth E],
H [auth F],
I [auth G],
J [auth H]
2N/A
Glycosylation Resources
GlyTouCan:  G07411ON
GlyCosmos:  G07411ON
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.55 Å
  • R-Value Free: 0.314 
  • R-Value Work: 0.273 
  • R-Value Observed: 0.275 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 72.26α = 90
b = 130.743β = 90
c = 308.519γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
PDB_EXTRACTdata extraction
Cootmodel building
Omodel building
PHASERphasing
XDSdata reduction
SCALAdata scaling

Structure Validation

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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2015-03-04
    Type: Initial release
  • Version 1.1: 2015-07-29
    Changes: Database references, Source and taxonomy
  • Version 2.0: 2020-07-29
    Type: Remediation
    Reason: Carbohydrate remediation
    Changes: Advisory, Atomic model, Data collection, Derived calculations, Non-polymer description, Source and taxonomy, Structure summary
  • Version 2.1: 2024-02-28
    Changes: Data collection, Database references, Structure summary