2AXL

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

Summary for 2AXL

• Entry DOI: 10.2210/pdb2axl/pdb
• NMR Information: BMRB: 6540
• Descriptor: Werner syndrome (1 entity in total)
• Functional Keywords: the wh-like domain, dna binding protein, protein binding
• Biological source: Homo sapiens (human)
• Cellular location: Nucleus, nucleolus: Q14191
• Total number of polymer chains: 1
• Total formula weight: 16428.71

Authors

Hu, J.-S.,Feng, H.,Zeng, W.,Lin, G.-X.,Xi, X.G. (deposition date: 2005-09-05, release date: 2005-12-13, Last modification date: 2024-05-22)

Primary citation

Hu, J.-S.,Feng, H.,Zeng, W.,Lin, G.-X.,Xi, X.G.
Solution structure of a multifunctional DNA- and protein-binding motif of human Werner syndrome protein.
Proc.Natl.Acad.Sci.Usa, 102:18379-18384, 2005

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

PubMed: 16339893
DOI: 10.1073/pnas.0509380102

Experimental method

SOLUTION NMR