This old version of Proteopedia is provided for student assignments while the new version is undergoing repairs. Content and edits done in this old version of Proteopedia after March 1, 2026 will eventually be lost when it is retired in about June of 2026.

Apply for new accounts at the new Proteopedia. Your logins will work in both the old and new versions.

2e1e

From Proteopedia

(Difference between revisions)

Jump to: navigation, search

Revision as of 06:59, 6 June 2018

Crystal structure of the HRDC Domain of Human Werner Syndrome Protein, WRN

Structural highlights

2e1e is a 1 chain structure with sequence from Human. Full crystallographic information is available from OCA. For a guided tour on the structure components use FirstGlance.
Ligands:
Related:	2e1f
Resources:	FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT

Disease

[WRN_HUMAN] Defects in WRN are a cause of Werner syndrome (WRN) [MIM: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.^[1] Defects in WRN may be a cause of colorectal cancer (CRC) [MIM:114500].

Function

[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).^[2] ^[3] ^[4] ^[5] ^[6]

Evolutionary Conservation

Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf.

Publication Abstract from PubMed

Werner syndrome is a human premature aging disorder characterized by chromosomal instability. The disease is caused by the functional loss of WRN, a member of the RecQ-helicase family that plays an important role in DNA metabolic pathways. WRN contains four structurally folded domains comprising an exonuclease, a helicase, a winged-helix, and a helicase-and-ribonuclease D/C-terminal (HRDC) domain. In contrast to the accumulated knowledge pertaining to the biochemical functions of the three N-terminal domains, the function of C-terminal HRDC remains unknown. In this study, the crystal structure of the human WRN HRDC domain has been determined. The domain forms a bundle of alpha-helices similar to those of Saccharomyces cerevisiae Sgs1 and Escherichia coli RecQ. Surprisingly, the extra ten residues at each of the N and C termini of the domain were found to participate in the domain architecture by forming an extended portion of the first helix alpha1, and a novel looping motif that traverses straight along the domain surface, respectively. The motifs combine to increase the domain surface of WRN HRDC, which is larger than that of Sgs1 and E. coli. In WRN HRDC, neither of the proposed DNA-binding surfaces in Sgs1 or E. coli is conserved, and the domain was shown to lack DNA-binding ability in vitro. Moreover, the domain was shown to be thermostable and resistant to protease digestion, implying independent domain evolution in WRN. Coupled with the unique long linker region in WRN, the WRN HRDC may be adapted to play a distinct function in WRN that involves protein-protein interactions.

Crystal structure of the HRDC domain of human Werner syndrome protein, WRN.,Kitano K, Yoshihara N, Hakoshima T J Biol Chem. 2007 Jan 26;282(4):2717-28. Epub 2006 Dec 4. PMID:17148451^[7]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.

References

↑ Huang S, Lee L, Hanson NB, Lenaerts C, Hoehn H, Poot M, Rubin CD, Chen DF, Yang CC, Juch H, Dorn T, Spiegel R, Oral EA, Abid M, Battisti C, Lucci-Cordisco E, Neri G, Steed EH, Kidd A, Isley W, Showalter D, Vittone JL, Konstantinow A, Ring J, Meyer P, Wenger SL, von Herbay A, Wollina U, Schuelke M, Huizenga CR, Leistritz DF, Martin GM, Mian IS, Oshima J. The spectrum of WRN mutations in Werner syndrome patients. Hum Mutat. 2006 Jun;27(6):558-67. PMID:16673358 doi:10.1002/humu.20337
↑ Xue Y, Ratcliff GC, Wang H, Davis-Searles PR, Gray MD, Erie DA, Redinbo MR. A minimal exonuclease domain of WRN forms a hexamer on DNA and possesses both 3'- 5' exonuclease and 5'-protruding strand endonuclease activities. Biochemistry. 2002 Mar 5;41(9):2901-12. PMID:11863428
↑ Kamath-Loeb AS, Lan L, Nakajima S, Yasui A, Loeb LA. Werner syndrome protein interacts functionally with translesion DNA polymerases. Proc Natl Acad Sci U S A. 2007 Jun 19;104(25):10394-9. Epub 2007 Jun 11. PMID:17563354 doi:10.1073/pnas.0702513104
↑ Compton SA, Tolun G, Kamath-Loeb AS, Loeb LA, Griffith JD. The Werner syndrome protein binds replication fork and holliday junction DNAs as an oligomer. J Biol Chem. 2008 Sep 5;283(36):24478-83. doi: 10.1074/jbc.M803370200. Epub 2008 , Jul 2. PMID:18596042 doi:10.1074/jbc.M803370200
↑ Zecevic A, Menard H, Gurel V, Hagan E, DeCaro R, Zhitkovich A. WRN helicase promotes repair of DNA double-strand breaks caused by aberrant mismatch repair of chromium-DNA adducts. Cell Cycle. 2009 Sep 1;8(17):2769-78. Epub 2009 Sep 2. PMID:19652551
↑ Opresko PL, Sowd G, Wang H. The Werner syndrome helicase/exonuclease processes mobile D-loops through branch migration and degradation. PLoS One. 2009;4(3):e4825. doi: 10.1371/journal.pone.0004825. Epub 2009 Mar 13. PMID:19283071 doi:10.1371/journal.pone.0004825
↑ Kitano K, Yoshihara N, Hakoshima T. Crystal structure of the HRDC domain of human Werner syndrome protein, WRN. J Biol Chem. 2007 Jan 26;282(4):2717-28. Epub 2006 Dec 4. PMID:17148451 doi:10.1074/jbc.M610142200

1 Structural highlights
2 Disease
3 Function
4 Evolutionary Conservation
5 Publication Abstract from PubMed
6 See Also
7 References

Proteopedia Page Contributors and Editors (what is this?)

OCA

Retrieved from "http://52.214.119.220/wiki/index.php/2e1e"

@@ Line 1: / Line 1: @@
 ==Crystal structure of the HRDC Domain of Human Werner Syndrome Protein, WRN==
 <StructureSection load='2e1e' size='340' side='right' caption='[[2e1e]], [[Resolution|resolution]] 2.30&Aring;' scene=''>
@@ Line 5: / Line 6: @@
 </td></tr><tr id='ligand'><td class="sblockLbl"><b>[[Ligand|Ligands:]]</b></td><td class="sblockDat"><scene name='pdbligand=CL:CHLORIDE+ION'>CL</scene></td></tr>
 <tr id='related'><td class="sblockLbl"><b>[[Related_structure|Related:]]</b></td><td class="sblockDat">[[2e1f|2e1f]]</td></tr>
-<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2e1e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2e1e OCA], [http://pdbe.org/2e1e PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2e1e RCSB], [http://www.ebi.ac.uk/pdbsum/2e1e PDBsum]</span></td></tr>
+<tr id='resources'><td class="sblockLbl"><b>Resources:</b></td><td class="sblockDat"><span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2e1e FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2e1e OCA], [http://pdbe.org/2e1e PDBe], [http://www.rcsb.org/pdb/explore.do?structureId=2e1e RCSB], [http://www.ebi.ac.uk/pdbsum/2e1e PDBsum], [http://prosat.h-its.org/prosat/prosatexe?pdbcode=2e1e ProSAT]</span></td></tr>
 </table>
 == Disease ==
@@ Line 15: / Line 16: @@
 Check<jmol>
   <jmolCheckbox>
-    <scriptWhenChecked>select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/e1/2e1e_consurf.spt"</scriptWhenChecked>
+    <scriptWhenChecked>; select protein; define ~consurf_to_do selected; consurf_initial_scene = true; script "/wiki/ConSurf/e1/2e1e_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/chain_selection.php?pdb_ID=2ata ConSurf].
+</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=2e1e ConSurf].
 <div style="clear:both"></div>
 <div style="background-color:#fffaf0;">

2e1e

From Proteopedia

Revision as of 06:59, 6 June 2018

Crystal structure of the HRDC Domain of Human Werner Syndrome Protein, WRN

Structural highlights

Disease

Function

Evolutionary Conservation

Publication Abstract from PubMed

See Also

References

Contents

Proteopedia Page Contributors and Editors (what is this?)

Views

Personal tools

Navigation

Search

Toolbox