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PDBsum entry 2axl

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protein links
DNA binding protein, protein binding PDB id
2axl
Jmol
Contents
Protein chain
144 a.a. *
* Residue conservation analysis
PDB id:
2axl
Name: DNA binding protein, protein binding
Title: Solution structure of a multifunctional DNA- and protein- binding domain of human werner syndrome protein
Structure: Werner syndrome. Chain: a. Fragment: the dpbd. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Expressed in: escherichia coli bl21. Expression_system_taxid: 511693.
NMR struc: 10 models
Authors: J.-S.Hu,H.Feng,W.Zeng,G.-X.Lin,X.G.Xi
Key ref:
J.S.Hu et al. (2005). Solution structure of a multifunctional DNA- and protein-binding motif of human Werner syndrome protein. Proc Natl Acad Sci U S A, 102, 18379-18384. PubMed id: 16339893 DOI: 10.1073/pnas.0509380102
Date:
05-Sep-05     Release date:   13-Dec-05    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
Q14191  (WRN_HUMAN) -  Werner syndrome ATP-dependent helicase
Seq:
Struc:
 
Seq:
Struc:
 
Seq:
Struc:
1432 a.a.
144 a.a.
Key:    PfamA domain  PfamB domain  Secondary structure  CATH domain

 Enzyme reactions 
   Enzyme class: E.C.3.6.4.12  - Dna helicase.
[IntEnz]   [ExPASy]   [KEGG]   [BRENDA]
      Reaction: ATP + H2O = ADP + phosphate
ATP
+ H(2)O
= ADP
+ phosphate
Molecule diagrams generated from .mol files obtained from the KEGG ftp site
 Gene Ontology (GO) functional annotation 
  GO annot!
  Biological process     DNA repair   2 terms 
  Biochemical function     ATP-dependent 3'-5' DNA helicase activity     1 term  

 

 
    reference    
 
 
DOI no: 10.1073/pnas.0509380102 Proc Natl Acad Sci U S A 102:18379-18384 (2005)
PubMed id: 16339893  
 
 
Solution structure of a multifunctional DNA- and protein-binding motif of human Werner syndrome protein.
J.S.Hu, H.Feng, W.Zeng, G.X.Lin, X.G.Xi.
 
  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.
 
  Selected figure(s)  
 
Figure 1.
Fig. 1. Secondary structure of the DPBD of WRN and sequence alignments of WT DPBD with five WS-associated mutants. WS1, IVS25-1G C mutation in the last base of intron 25 (4); WS2, IVS26+1G C mutation in the first base of intron 26 (10). WS1 and WS2 give an identical protein, and only WS1 is shown. WS3, 3265-3266delGA mutation in exon 25 (10); WS4, 3259-3262delCAAA mutation in exon 25 (10); WS5, 3004delG mutation in exon 23 (11). The modified sequences in the mutants are highlighted in pink.
Figure 6.
Fig. 6. Model for the regulation of the WRN enzyme by DPBD. Only three functional domains, helicase core (HC), putative Zn-binding domain (ZBD), and DPBD, of WRN are shown. The active site of HC is shown. The DPBD has the strongest DNA-binding pocket of WRN, which collaborates with ZBD to form an even stronger DNA-binding site to hold on to the upstream duplex region of a DNA substrate, whereas HC unwinds at the fork junction of the DNA substrate. The DPBD-DNA interaction dictates a specific DNA processing pathway. The protein-protein interaction between DPBD and the regulatory proteins as discussed in the text directs the cellular localization of WRN or regulates the enzymatic activity of HC.
 
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
20159463 K.Kitano, S.Y.Kim, and T.Hakoshima (2010).
Structural basis for DNA strand separation by the unconventional winged-helix domain of RecQ helicase WRN.
  Structure, 18, 177-187.
PDB code: 3aaf
20639533 Y.M.Kim, and B.S.Choi (2010).
Structure and function of the regulatory HRDC domain from human Bloom syndrome protein.
  Nucleic Acids Res, 38, 7764-7777.
PDB code: 2kv2
19151156 A.C.Pike, B.Shrestha, V.Popuri, N.Burgess-Brown, L.Muzzolini, S.Costantini, A.Vindigni, and O.Gileadi (2009).
Structure of the human RECQ1 helicase reveals a putative strand-separation pin.
  Proc Natl Acad Sci U S A, 106, 1039-1044.
PDB code: 2v1x
19949442 A.Vindigni, and I.D.Hickson (2009).
RecQ helicases: multiple structures for multiple functions?
  HFSP J, 3, 153-164.  
19017267 M.P.Killoran, P.L.Kohler, J.P.Dillard, and J.L.Keck (2009).
RecQ DNA helicase HRDC domains are critical determinants in Neisseria gonorrhoeae pilin antigenic variation and DNA repair.
  Mol Microbiol, 71, 158-171.  
19150358 R.D.Shereda, N.J.Reiter, S.E.Butcher, and J.L.Keck (2009).
Identification of the SSB binding site on E. coli RecQ reveals a conserved surface for binding SSB's C terminus.
  J Mol Biol, 386, 612-625.  
18411208 M.P.Killoran, and J.L.Keck (2008).
Structure and function of the regulatory C-terminal HRDC domain from Deinococcus radiodurans RecQ.
  Nucleic Acids Res, 36, 3139-3149.
PDB code: 2rhf
18937104 R.D.Shereda, A.G.Kozlov, T.M.Lohman, M.M.Cox, and J.L.Keck (2008).
SSB as an organizer/mobilizer of genome maintenance complexes.
  Crit Rev Biochem Mol Biol, 43, 289-318.  
  18473724 R.Gupta, and R.M.Brosh (2008).
Helicases as prospective targets for anti-cancer therapy.
  Anticancer Agents Med Chem, 8, 390-401.  
18441481 T.Katsuya, H.Rakugi, and T.Ogihara (2008).
[Senescence gene and anti-aging medicine]
  Nippon Ronen Igakkai Zasshi, 45, 141-144.  
17174478 J.J.Perry, L.Fan, and J.A.Tainer (2007).
Developing master keys to brain pathology, cancer and aging from the structural biology of proteins controlling reactive oxygen species and DNA repair.
  Neuroscience, 145, 1280-1299.  
16935877 M.P.Killoran, and J.L.Keck (2006).
Sit down, relax and unwind: structural insights into RecQ helicase mechanisms.
  Nucleic Acids Res, 34, 4098-4105.  
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.