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2axl
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Revision as of 18:49, 12 November 2007
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Solution structure of a multifunctional DNA- and protein-binding domain of human Werner syndrome protein
Contents |
Overview
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.
Disease
Known diseases associated with this structure: Werner syndrome OMIM:[604611]
About this Structure
2AXL is a Single protein structure of sequence from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Solution structure of a multifunctional DNA- and protein-binding motif of human Werner syndrome protein., Hu JS, Feng H, Zeng W, Lin GX, Xi XG, Proc Natl Acad Sci U S A. 2005 Dec 20;102(51):18379-84. Epub 2005 Dec 9. PMID:16339893
Page seeded by OCA on Mon Nov 12 20:55:59 2007
