2JPA

Structure of the Wilms Tumor Suppressor Protein Zinc Finger Domain Bound to DNA


Experimental Data Snapshot

  • Method: SOLUTION NMR
  • Conformers Calculated: 200 
  • Conformers Submitted: 20 
  • Selection Criteria: structures with the lowest energy 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Structure of the wilms tumor suppressor protein zinc finger domain bound to DNA

Stoll, R.Lee, B.M.Debler, E.W.Laity, J.H.Wilson, I.A.Dyson, H.J.Wright, P.E.

(2007) J Mol Biol 372: 1227-1245

  • DOI: https://doi.org/10.1016/j.jmb.2007.07.017
  • Primary Citation of Related Structures:  
    2JP9, 2JPA, 2PRT

  • PubMed Abstract: 

    The zinc finger domain of the Wilms tumor suppressor protein (WT1) contains four canonical Cys(2)His(2) zinc fingers. WT1 binds preferentially to DNA sequences that are closely related to the EGR-1 consensus site. We report the structure determination by both X-ray crystallography and NMR spectroscopy of the WT1 zinc finger domain in complex with DNA. The X-ray structure was determined for the complex with a cognate 14 base-pair oligonucleotide, and composite X-ray/NMR structures were determined for complexes with both the 14 base-pair and an extended 17 base-pair DNA. This combined approach allowed unambiguous determination of the position of the first zinc finger, which is influenced by lattice contacts in the crystal structure. The crystal structure shows the second, third and fourth zinc finger domains inserted deep into the major groove of the DNA where they make base-specific interactions. The DNA duplex is distorted in the vicinity of the first zinc finger, with a cytidine twisted and tilted out of the base stack to pack against finger 1 and the tip of finger 2. By contrast, the composite X-ray/NMR structures show that finger 1 continues to follow the major groove in the solution complexes. However, the orientation of the helix is non-canonical, and the fingertip and the N terminus of the helix project out of the major groove; as a consequence, the zinc finger side-chains that are commonly involved in base recognition make no contact with the DNA. We conclude that finger 1 helps to anchor WT1 to the DNA by amplifying the binding affinity although it does not contribute significantly to binding specificity. The structures provide molecular level insights into the potential consequences of mutations in zinc fingers 2 and 3 that are associated with Denys-Drash syndrome and nephritic syndrome. The mutations are of two types, and either destabilize the zinc finger structure or replace key base contact residues.


  • Organizational Affiliation

    Department of Molecular Biology and Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.


Macromolecules

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Entity ID: 3
MoleculeChains Sequence LengthOrganismDetailsImage
Wilms tumor 1C [auth A]119Homo sapiensMutation(s): 0 
Gene Names: WT1
UniProt & NIH Common Fund Data Resources
Find proteins for P19544 (Homo sapiens)
Explore P19544 
Go to UniProtKB:  P19544
PHAROS:  P19544
GTEx:  ENSG00000184937 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP19544
Sequence Annotations
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  • Reference Sequence

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Entity ID: 1
MoleculeChains LengthOrganismImage
DNA (5'-D(P*DCP*DGP*DCP*DGP*DGP*DGP*DGP*DGP*DCP*DGP*DTP*DCP*DTP*DG)-3')A [auth B]14synthetic construct
Sequence Annotations
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  • Reference Sequence

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Entity ID: 2
MoleculeChains LengthOrganismImage
DNA (5'-D(P*DCP*DAP*DGP*DAP*DCP*DGP*DCP*DCP*DCP*DCP*DCP*DGP*DCP*DG)-3')B [auth C]14synthetic construct
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: SOLUTION NMR
  • Conformers Calculated: 200 
  • Conformers Submitted: 20 
  • Selection Criteria: structures with the lowest energy 

Structure Validation

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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2007-10-30
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2020-02-05
    Changes: Data collection, Database references, Derived calculations, Experimental preparation, Other, Source and taxonomy
  • Version 1.3: 2024-05-01
    Changes: Data collection, Database references, Derived calculations