Solution structure of a multifunctional DNA- and protein-binding motif of human Werner syndrome protein.

作者: J.-S. Hu , H. Feng , W. Zeng , G.-x. Lin , X. G. Xi

DOI: 10.1073/PNAS.0509380102

关键词: RecQ helicaseCellular localizationGeneticsPremature agingWerner Syndrome HelicaseBiologyProtein structureWerner syndromeDNA replicationHelicase

摘要: Werner syndrome (WS) is an autosomal recessive disease that results in premature aging. Mutations the WS gene (WRN) result a loss of expression WRN protein and predispose patients to accelerated As helicase nuclease, unique among five human RecQ family members capable multiple functions involved DNA replication, repair, recombination, telomere maintenance. A 144-residue fragment was previously determined be multifunctional DNA- protein-binding domain (DPBD) interacts with structure-specific variety DNA-processing proteins. In addition, DPBD as nucleolar targeting sequence WRN. The solution structure DPBD, first fragment, has been solved by NMR. consists winged helix-like motif unstructured C-terminal region ≈20 aa. putative DNA-binding surface identified using known structural biochemical data. Based on data data, we suggest for interacting other this model, single helix binds both Furthermore, propose regulatory regulate enzymatic activity direct cellular localization through protein–protein interaction.

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