4JGV

Crystal Structure of Human Nur77 Ligand-binding Domain in Complex with THPN


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.01 Å
  • R-Value Free: 0.256 
  • R-Value Work: 0.178 
  • R-Value Observed: 0.182 

wwPDB Validation   3D Report Full Report


Ligand Structure Quality Assessment 


This is version 1.2 of the entry. See complete history


Literature

Orphan nuclear receptor TR3 acts in autophagic cell death via mitochondrial signaling pathway.

Wang, W.Wang, Y.Chen, H.Xing, Y.Li, F.Zhang, Q.Zhou, B.Zhang, H.Zhang, J.Bian, X.Li, L.Liu, Y.Zhao, B.Chen, Y.Wu, R.Li, A.Yao, L.Chen, P.Zhang, Y.Tian, X.Beermann, F.Wu, M.Han, J.Huang, P.Lin, T.Wu, Q.

(2014) Nat Chem Biol 10: 133-140

  • DOI: https://doi.org/10.1038/nchembio.1406
  • Primary Citation of Related Structures:  
    4JGV, 4KZI, 4KZJ, 4KZM

  • PubMed Abstract: 

    Autophagy is linked to cell death, yet the associated mechanisms are largely undercharacterized. We discovered that melanoma, which is generally resistant to drug-induced apoptosis, can undergo autophagic cell death with the participation of orphan nuclear receptor TR3. A sequence of molecular events leading to cellular demise is launched by a specific chemical compound, 1-(3,4,5-trihydroxyphenyl)nonan-1-one, newly acquired from screening a library of TR3-targeting compounds. The autophagic cascade comprises TR3 translocation to mitochondria through interaction with the mitochondrial outer membrane protein Nix, crossing into the mitochondrial inner membrane through Tom40 and Tom70 channel proteins, dissipation of mitochondrial membrane potential by the permeability transition pore complex ANT1-VDAC1 and induction of autophagy. This process leads to excessive mitochondria clearance and irreversible cell death. It implicates a new approach to melanoma therapy through activation of a mitochondrial signaling pathway that integrates a nuclear receptor with autophagy for cell death.


  • Organizational Affiliation

    1] State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Biology, School of Life Sciences, Xiamen University, Xiamen, Fujian Province, China. [2].


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Nuclear receptor subfamily 4 group A member 1
A, B
249Homo sapiensMutation(s): 0 
Gene Names: NR4A1GFRP1HMRNAK1
UniProt & NIH Common Fund Data Resources
Find proteins for P22736 (Homo sapiens)
Explore P22736 
Go to UniProtKB:  P22736
PHAROS:  P22736
GTEx:  ENSG00000123358 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP22736
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Binding Affinity Annotations 
IDSourceBinding Affinity
T94 PDBBind:  4JGV Kd: 270 (nM) from 1 assay(s)
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.01 Å
  • R-Value Free: 0.256 
  • R-Value Work: 0.178 
  • R-Value Observed: 0.182 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 74.084α = 90
b = 76.9β = 90
c = 128.137γ = 90
Software Package:
Software NamePurpose
HKL-2000data collection
PHASERphasing
REFMACrefinement
HKL-2000data reduction
HKL-2000data scaling

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2013-12-18
    Type: Initial release
  • Version 1.1: 2014-03-19
    Changes: Database references
  • Version 1.2: 2024-03-20
    Changes: Data collection, Database references, Derived calculations, Refinement description