2axl
From Proteopedia
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'''Solution structure of a multifunctional DNA- and protein-binding domain of human Werner syndrome protein'''<br /> | '''Solution structure of a multifunctional DNA- and protein-binding domain of human Werner syndrome protein'''<br /> | ||
==Overview== | ==Overview== | ||
| - | Werner syndrome (WS) is an autosomal recessive disease that results in | + | 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== | ==Disease== | ||
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==About this Structure== | ==About this Structure== | ||
| - | 2AXL is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http:// | + | 2AXL is a [http://en.wikipedia.org/wiki/Single_protein Single protein] structure of sequence from [http://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2AXL OCA]. |
==Reference== | ==Reference== | ||
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[[Category: Single protein]] | [[Category: Single protein]] | ||
[[Category: Feng, H.]] | [[Category: Feng, H.]] | ||
| - | [[Category: Hu, J | + | [[Category: Hu, J S.]] |
| - | [[Category: Lin, G | + | [[Category: Lin, G X.]] |
| - | [[Category: Xi, X | + | [[Category: Xi, X G.]] |
[[Category: Zeng, W.]] | [[Category: Zeng, W.]] | ||
[[Category: the wh-like domain]] | [[Category: the wh-like domain]] | ||
| - | ''Page seeded by [http:// | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 16:32:02 2008'' |
Revision as of 14:32, 21 February 2008
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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
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