2FBT

WRN exonuclease

2FBT の概要

• エントリーDOI: 10.2210/pdb2fbt/pdb
• 分子名称: Werner syndrome helicase, ACETIC ACID (3 entities in total)
• 機能のキーワード: recq, wrn, werner syndrome, 3'-5' exonuclease, dnaq family, transferase
• 由来する生物種: Homo sapiens (human)
• 細胞内の位置: Nucleus, nucleolus: Q14191
• タンパク質・核酸の鎖数: 1
• 化学式量合計: 23490.92

構造登録者

Perry, J.J. (登録日: 2005-12-10, 公開日: 2006-04-25, 最終更新日: 2024-04-03)

主引用文献

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

実験手法

X-RAY DIFFRACTION (2.05 Å)