2FBX

WRN exonuclease, Mg complex

Summary for 2FBX

• Entry DOI: 10.2210/pdb2fbx/pdb
• Related: 2FBT 2FBV 2FBY 2FC0
• Descriptor: Werner syndrome helicase, MAGNESIUM ION (3 entities in total)
• Functional Keywords: recq, wrn, werner syndrome, 3'-5' exonuclease, dnaq family, transferase
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus, nucleolus : Q14191
• Total number of polymer chains: 1
• Total formula weight: 23479.48

Authors

Perry, J.J. (deposition date: 2005-12-10, release date: 2006-04-25, Last modification date: 2023-08-30)

Primary citation

Perry, J.J.,Yannone, S.M.,Holden, L.G.,Hitomi, C.,Asaithamby, A.,Han, S.,Cooper, P.K.,Chen, D.J.,Tainer, J.A.
WRN exonuclease structure and molecular mechanism imply an editing role in DNA end processing.
Nat.Struct.Mol.Biol., 13:414-422, 2006

PubMed Abstract: WRN is unique among the five human RecQ DNA helicases in having a functional exonuclease domain (WRN-exo) and being defective in the premature aging and cancer-related disorder Werner syndrome. Here, we characterize WRN-exo crystal structures, biochemical activity and participation in DNA end joining. Metal-ion complex structures, active site mutations and activity assays reveal a nuclease mechanism mediated by two metal ions. The DNA end-binding Ku70/80 complex specifically stimulates WRN-exo activity, and structure-based mutational inactivation of WRN-exo alters DNA end joining in human cells. We furthermore establish structural and biochemical similarities of WRN-exo to DnaQ-family replicative proofreading exonucleases, describing WRN-specific adaptations consistent with double-stranded DNA specificity and functionally important conformational changes. These results indicate WRN-exo is a human DnaQ family member and support DnaQ-like proofreading activities stimulated by Ku70/80, with implications for WRN functions in age-related pathologies and maintenance of genomic integrity.

PubMed: 16622405
DOI: 10.1038/nsmb1088

Experimental method

X-RAY DIFFRACTION (2.2 Å)