2JTG

Solution structure of the THAP-zinc finger of THAP1


Experimental Data Snapshot

  • Method: SOLUTION NMR
  • Conformers Calculated: 500 
  • Conformers Submitted: 20 
  • Selection Criteria: structures with the lowest energy 

wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

Structure-function analysis of the THAP zinc finger of THAP1, a large C2CH DNA-binding module linked to Rb/E2F pathways

Bessiere, D.Lacroix, C.Campagne, S.Ecochard, V.Guillet, V.Mourey, L.Lopez, F.Czaplicki, J.Demange, P.Milon, A.Girard, J.P.Gervais, V.

(2008) J Biol Chem 283: 4352-4363

  • DOI: https://doi.org/10.1074/jbc.M707537200
  • Primary Citation of Related Structures:  
    2JTG

  • PubMed Abstract: 

    THAP1, the founding member of a previously uncharacterized large family of cellular proteins (THAP proteins), is a sequence-specific DNA-binding factor that has recently been shown to regulate cell proliferation through modulation of pRb/E2F cell cycle target genes. THAP1 shares its DNA-binding THAP zinc finger domain with Drosophila P element transposase, zebrafish E2F6, and several nematode proteins interacting genetically with the retinoblastoma protein pRb. In this study, we report the three-dimensional structure and structure-function relationships of the THAP zinc finger of human THAP1. Deletion mutagenesis and multidimensional NMR spectroscopy revealed that the THAP domain of THAP1 is an atypical zinc finger of approximately 80 residues, distinguished by the presence between the C2CH zinc coordinating residues of a short antiparallel beta-sheet interspersed by a long loop-helix-loop insertion. Alanine scanning mutagenesis of this loop-helix-loop motif resulted in the identification of a number of critical residues for DNA recognition. NMR chemical shift perturbation analysis was used to further characterize the residues involved in DNA binding. The combination of the mutagenesis and NMR data allowed the mapping of the DNA binding interface of the THAP zinc finger to a highly positively charged area harboring multiple lysine and arginine residues. Together, these data represent the first structure-function analysis of a functional THAP domain, with demonstrated sequence-specific DNA binding activity. They also provide a structural framework for understanding DNA recognition by this atypical zinc finger, which defines a novel family of cellular factors linked to cell proliferation and pRb/E2F cell cycle pathways in humans, fish, and nematodes.


  • Organizational Affiliation

    University of Toulouse, Institute of Pharmacology and Structural Biology, France.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
THAP domain-containing protein 187Homo sapiensMutation(s): 0 
Gene Names: THAP1
UniProt & NIH Common Fund Data Resources
Find proteins for Q9NVV9 (Homo sapiens)
Explore Q9NVV9 
Go to UniProtKB:  Q9NVV9
PHAROS:  Q9NVV9
GTEx:  ENSG00000131931 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ9NVV9
Sequence Annotations
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  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
ZN
Query on ZN

Download Ideal Coordinates CCD File 
B [auth A]ZINC ION
Zn
PTFCDOFLOPIGGS-UHFFFAOYSA-N
Experimental Data & Validation

Experimental Data

  • Method: SOLUTION NMR
  • Conformers Calculated: 500 
  • Conformers Submitted: 20 
  • Selection Criteria: structures with the lowest energy 

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2007-12-11
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2022-03-16
    Changes: Data collection, Database references, Derived calculations