View source for 2axl


==Solution structure of a multifunctional DNA- and protein-binding domain of human Werner syndrome protein==
<StructureSection load='2axl' size='340' side='right'caption='[[2axl]]' scene=''>
== Structural highlights ==
<table><tr><td colspan='2'>[[2axl]] is a 1 chain structure with sequence from [https://en.wikipedia.org/wiki/Homo_sapiens Homo sapiens]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2AXL OCA]. For a <b>guided tour on the structure components</b> use [https://proteopedia.org/fgij/fg.htm?mol=2AXL FirstGlance]. <br>
</td></tr><tr id='method'><td class="sblockLbl"><b>[[Empirical_models|Method:]]</b></td><td class="sblockDat" id="methodDat">Solution NMR</td></tr>
<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[https://proteopedia.org/fgij/fg.htm?mol=2axl FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2axl OCA], [https://pdbe.org/2axl PDBe], [https://www.rcsb.org/pdb/explore.do?structureId=2axl RCSB], [https://www.ebi.ac.uk/pdbsum/2axl PDBsum], [https://prosat.h-its.org/prosat/prosatexe?pdbcode=2axl ProSAT]</span></td></tr>
</table>
== Disease ==
[https://www.uniprot.org/uniprot/WRN_HUMAN WRN_HUMAN] Defects in WRN are a cause of Werner syndrome (WRN) [MIM:[https://omim.org/entry/277700 277700]. WRN is a rare autosomal recessive progeroid syndrome characterized by the premature onset of multiple age-related disorders, including atherosclerosis, cancer, non-insulin-dependent diabetes mellitus, ocular cataracts and osteoporosis. The major cause of death, at a median age of 47, is myocardial infarction. Currently all known WS mutations produces prematurely terminated proteins.<ref>PMID:16673358</ref>   Defects in WRN may be a cause of colorectal cancer (CRC) [MIM:[https://omim.org/entry/114500 114500].
== Function ==
[https://www.uniprot.org/uniprot/WRN_HUMAN WRN_HUMAN] Multifunctional enzyme that has both magnesium and ATP-dependent DNA-helicase activity and 3'->5' exonuclease activity towards double-stranded DNA with a 5'-overhang. Has no nuclease activity towards single-stranded DNA or blunt-ended double-stranded DNA. Binds preferentially to DNA substrates containing alternate secondary structures, such as replication forks and Holliday junctions. May play an important role in the dissociation of joint DNA molecules that can arise as products of homologous recombination, at stalled replication forks or during DNA repair. Alleviates stalling of DNA polymerases at the site of DNA lesions. Important for genomic integrity. Plays a role in the formation of DNA replication focal centers; stably associates with foci elements generating binding sites for RP-A (By similarity).<ref>PMID:11863428</ref> <ref>PMID:17563354</ref> <ref>PMID:18596042</ref> <ref>PMID:19652551</ref> <ref>PMID:19283071</ref> 
== Evolutionary Conservation ==
[[Image:Consurf_key_small.gif|200px|right]]
Check<jmol>
  <jmolCheckbox>
    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/ax/2axl_consurf.spt"</scriptWhenChecked>
    <scriptWhenUnchecked>script /wiki/extensions/Proteopedia/spt/initialview01.spt</scriptWhenUnchecked>
    <text>to colour the structure by Evolutionary Conservation</text>
  </jmolCheckbox>
</jmol>, as determined by [http://consurfdb.tau.ac.il/ ConSurfDB]. You may read the [[Conservation%2C_Evolutionary|explanation]] of the method and the full data available from [http://bental.tau.ac.il/new_ConSurfDB/main_output.php?pdb_ID=2axl ConSurf].
<div style="clear:both"></div>
<div style="background-color:#fffaf0;">
== Publication Abstract from PubMed ==
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.

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<ref>PMID:16339893</ref>

From MEDLINE&reg;/PubMed&reg;, a database of the U.S. National Library of Medicine.<br>
</div>
<div class="pdbe-citations 2axl" style="background-color:#fffaf0;"></div>
== References ==
<references/>
__TOC__
</StructureSection>
[[Category: Homo sapiens]]
[[Category: Large Structures]]
[[Category: Feng H]]
[[Category: Hu J-S]]
[[Category: Lin G-X]]
[[Category: Xi XG]]
[[Category: Zeng W]]