3II6

Structure of human Xrcc4 in complex with the tandem BRCT domains of DNA LigaseIV.


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.40 Å
  • R-Value Free: 0.280 
  • R-Value Work: 0.240 
  • R-Value Observed: 0.240 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Structural and functional interaction between the human DNA repair proteins DNA ligase IV and XRCC4

Wu, P.Y.Frit, P.Meesala, S.Dauvillier, S.Modesti, M.Andres, S.N.Huang, Y.Sekiguchi, J.Calsou, P.Salles, B.Junop, M.S.

(2009) Mol Cell Biol 11: 3163-3172

  • DOI: https://doi.org/10.1128/MCB.01895-08
  • Primary Citation of Related Structures:  
    3II6

  • PubMed Abstract: 

    Nonhomologous end-joining represents the major pathway used by human cells to repair DNA double-strand breaks. It relies on the XRCC4/DNA ligase IV complex to reseal DNA strands. Here we report the high-resolution crystal structure of human XRCC4 bound to the carboxy-terminal tandem BRCT repeat of DNA ligase IV. The structure differs from the homologous Saccharomyces cerevisiae complex and reveals an extensive DNA ligase IV binding interface formed by a helix-loop-helix structure within the inter-BRCT linker region, as well as significant interactions involving the second BRCT domain, which induces a kink in the tail region of XRCC4. We further demonstrate that interaction with the second BRCT domain of DNA ligase IV is necessary for stable binding to XRCC4 in cells, as well as to achieve efficient dominant-negative effects resulting in radiosensitization after ectopic overexpression of DNA ligase IV fragments in human fibroblasts. Together our findings provide unanticipated insight for understanding the physical and functional architecture of the nonhomologous end-joining ligation complex.


  • Organizational Affiliation

    CNRS, IPBS (Institut de Pharmacologie et de Biologie Structurale), Toulouse, France.


Macromolecules
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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
DNA repair protein XRCC4
A, B, C, D
203Homo sapiensMutation(s): 2 
Gene Names: XRCC4
UniProt & NIH Common Fund Data Resources
Find proteins for Q13426 (Homo sapiens)
Explore Q13426 
Go to UniProtKB:  Q13426
PHAROS:  Q13426
GTEx:  ENSG00000152422 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ13426
Sequence Annotations
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  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
DNA ligase 4E [auth X],
F [auth Y]
263Homo sapiensMutation(s): 0 
Gene Names: LIG4
EC: 6.5.1.1
UniProt & NIH Common Fund Data Resources
Find proteins for P49917 (Homo sapiens)
Explore P49917 
Go to UniProtKB:  P49917
PHAROS:  P49917
GTEx:  ENSG00000174405 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP49917
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.40 Å
  • R-Value Free: 0.280 
  • R-Value Work: 0.240 
  • R-Value Observed: 0.240 
  • Space Group: P 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 67.243α = 67.34
b = 85.982β = 82.86
c = 111.608γ = 74.52
Software Package:
Software NamePurpose
CNSrefinement
CrystalCleardata reduction
d*TREKdata scaling
CNSphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2009-08-11
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2021-10-13
    Changes: Database references, Derived calculations
  • Version 1.3: 2024-02-21
    Changes: Data collection