4UE8

Complex of D. melanogaster eIF4E with the 4E binding protein Thor


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.10 Å
  • R-Value Free: 0.161 
  • R-Value Work: 0.145 
  • R-Value Observed: 0.146 

Starting Model: experimental
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Ligand Structure Quality Assessment 

Created with Raphaël 2.3.0Worse 01 BetterLigand structure goodness of fit to experimental dataBest fitted P4GClick on this verticalbar to view details

This is version 1.3 of the entry. See complete history


Literature

Molecular Architecture of 4E-BP Translational Inhibitors Bound to Eif4E.

Peter, D.Igreja, C.Weber, R.Wohlbold, L.Weiler, C.Ebertsch, L.Weichenrieder, O.Izaurralde, E.

(2015) Mol Cell 57: 1074

  • DOI: https://doi.org/10.1016/j.molcel.2015.01.017
  • Primary Citation of Related Structures:  
    4UE8, 4UE9, 4UEA, 4UEB, 4UEC, 4UED

  • PubMed Abstract: 

    The eIF4E-binding proteins (4E-BPs) represent a diverse class of translation inhibitors that are often deregulated in cancer cells. 4E-BPs inhibit translation by competing with eIF4G for binding to eIF4E through an interface that consists of canonical and non-canonical eIF4E-binding motifs connected by a linker. The lack of high-resolution structures including the linkers, which contain phosphorylation sites, limits our understanding of how phosphorylation inhibits complex formation. Furthermore, the binding mechanism of the non-canonical motifs is poorly understood. Here, we present structures of human eIF4E bound to 4E-BP1 and fly eIF4E bound to Thor, 4E-T, and eIF4G. These structures reveal architectural elements that are unique to 4E-BPs and provide insight into the consequences of phosphorylation. Guided by these structures, we designed and crystallized a 4E-BP mimic that shows increased repressive activity. Our studies pave the way for the rational design of 4E-BP mimics as therapeutic tools to decrease translation during oncogenic transformation.


  • Organizational Affiliation

    Department of Biochemistry, Max Planck Institute for Developmental Biology, Spemannstrasse 35, 72076 Tübingen, Germany.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
EUKARYOTIC TRANSLATION INITIATION FACTOR 4E184Drosophila melanogasterMutation(s): 0 
UniProt
Find proteins for P48598 (Drosophila melanogaster)
Explore P48598 
Go to UniProtKB:  P48598
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP48598
Sequence Annotations
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  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
4E-BINDING PROTEIN THOR38Drosophila melanogasterMutation(s): 0 
UniProt
Find proteins for Q9XZ56 (Drosophila melanogaster)
Explore Q9XZ56 
Go to UniProtKB:  Q9XZ56
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ9XZ56
Sequence Annotations
Expand
  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.10 Å
  • R-Value Free: 0.161 
  • R-Value Work: 0.145 
  • R-Value Observed: 0.146 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 35.45α = 90
b = 73.29β = 112.49
c = 38.26γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
XDSdata reduction
XSCALEdata scaling
PHASERphasing

Structure Validation

View Full Validation Report



Ligand Structure Quality Assessment 

Created with Raphaël 2.3.0Worse 01 BetterLigand structure goodness of fit to experimental dataBest fitted P4GClick on this verticalbar to view details

Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2015-02-25
    Type: Initial release
  • Version 1.1: 2015-03-04
    Changes: Database references
  • Version 1.2: 2015-04-15
    Changes: Database references
  • Version 1.3: 2023-12-20
    Changes: Data collection, Database references, Derived calculations, Other, Refinement description