5U6Z

Crystal Structure of Xenopus laevis Apex2 C-terminal Znf-GRF Domain


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.60 Å
  • R-Value Free: 0.245 
  • R-Value Work: 0.195 
  • R-Value Observed: 0.200 

wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

APE2 Zf-GRF facilitates 3'-5' resection of DNA damage following oxidative stress.

Wallace, B.D.Berman, Z.Mueller, G.A.Lin, Y.Chang, T.Andres, S.N.Wojtaszek, J.L.DeRose, E.F.Appel, C.D.London, R.E.Yan, S.Williams, R.S.

(2017) Proc Natl Acad Sci U S A 114: 304-309

  • DOI: https://doi.org/10.1073/pnas.1610011114
  • Primary Citation of Related Structures:  
    5U6Z

  • PubMed Abstract: 

    The Xenopus laevis APE2 (apurinic/apyrimidinic endonuclease 2) nuclease participates in 3'-5' nucleolytic resection of oxidative DNA damage and activation of the ATR-Chk1 DNA damage response (DDR) pathway via ill-defined mechanisms. Here we report that APE2 resection activity is regulated by DNA interactions in its Zf-GRF domain, a region sharing high homology with DDR proteins Topoisomerase 3α (TOP3α) and NEIL3 (Nei-like DNA glycosylase 3), as well as transcription and RNA regulatory proteins, such as TTF2 (transcription termination factor 2), TFIIS, and RPB9. Biochemical and NMR results establish the nucleic acid-binding activity of the Zf-GRF domain. Moreover, an APE2 Zf-GRF X-ray structure and small-angle X-ray scattering analyses show that the Zf-GRF fold is typified by a crescent-shaped ssDNA binding claw that is flexibly appended to an APE2 endonuclease/exonuclease/phosphatase (EEP) catalytic core. Structure-guided Zf-GRF mutations impact APE2 DNA binding and 3'-5' exonuclease processing, and also prevent efficient APE2-dependent RPA recruitment to damaged chromatin and activation of the ATR-Chk1 DDR pathway in response to oxidative stress in Xenopus egg extracts. Collectively, our data unveil the APE2 Zf-GRF domain as a nucleic acid interaction module in the regulation of a key single-strand break resection function of APE2, and also reveal topologic similarity of the Zf-GRF to the zinc ribbon domains of TFIIS and RPB9.


  • Organizational Affiliation

    Genome Integrity and Structural Biology Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Department of Health and Human Services, Research Triangle Park, NC 27709.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
DNA-(apurinic or apyrimidinic site) lyase75Xenopus laevisMutation(s): 0 
Gene Names: apex2apex2-prov
EC: 4.2.99.18
UniProt
Find proteins for Q6DDT4 (Xenopus laevis)
Explore Q6DDT4 
Go to UniProtKB:  Q6DDT4
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ6DDT4
Sequence Annotations
Expand
  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.60 Å
  • R-Value Free: 0.245 
  • R-Value Work: 0.195 
  • R-Value Observed: 0.200 
  • Space Group: I 4
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 90.332α = 90
b = 90.332β = 90
c = 23.105γ = 90
Software Package:
Software NamePurpose
SCALEPACKdata scaling
PHENIXrefinement
PDB_EXTRACTdata extraction
HKL-3000data reduction
PHENIXphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2017-01-11
    Type: Initial release
  • Version 1.1: 2017-01-25
    Changes: Database references
  • Version 1.2: 2024-03-06
    Changes: Data collection, Database references