2OA8

Crystal Structure of mTREX1 with ssDNA


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.10 Å
  • R-Value Free: 0.259 
  • R-Value Work: 0.192 
  • R-Value Observed: 0.195 

wwPDB Validation   3D Report Full Report


This is version 1.4 of the entry. See complete history


Literature

The Crystal Structure of TREX1 Explains the 3' Nucleotide Specificity and Reveals a Polyproline II Helix for Protein Partnering.

de Silva, U.Choudhury, S.Bailey, S.L.Harvey, S.Perrino, F.W.Hollis, T.

(2007) J Biol Chem 282: 10537-10543

  • DOI: https://doi.org/10.1074/jbc.M700039200
  • Primary Citation of Related Structures:  
    2IOC, 2OA8

  • PubMed Abstract: 

    The TREX1 enzyme processes DNA ends as the major 3' --> 5' exonuclease activity in human cells. Mutations in the TREX1 gene are an underlying cause of the neurological brain disease Aicardi-Goutières syndrome implicating TREX1 dysfunction in an aberrant immune response. TREX1 action during apoptosis likely prevents autoimmune reaction to DNA that would otherwise persist. To understand the impact of TREX1 mutations identified in patients with Aicardi-Goutières syndrome on structure and activity we determined the x-ray crystal structure of the dimeric mouse TREX1 protein in substrate and product complexes containing single-stranded DNA and deoxyadenosine monophosphate, respectively. The structures show the specific interactions between the bound nucleotides and the residues lining the binding pocket of the 3' terminal nucleotide within the enzyme active site that account for specificity, and provide the molecular basis for understanding mutations that lead to disease. Three mutant forms of TREX1 protein identified in patients with Aicardi-Goutières syndrome were prepared and the measured activities show that these specific mutations reduce enzyme activity by 4-35,000-fold. The structure also reveals an 8-amino acid polyproline II helix within the TREX1 enzyme that suggests a mechanism for interactions of this exonuclease with other protein complexes.


  • Organizational Affiliation

    Department of Biochemistry, Center for Structural Biology, Wake Forest University Health Sciences, Winston-Salem, North Carolina 27157.


Macromolecules

Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Three prime repair exonuclease 1C [auth A],
D [auth B]
233Mus musculusMutation(s): 2 
Gene Names: Trex1
EC: 3.1.11.2
UniProt
Find proteins for Q91XB0 (Mus musculus)
Explore Q91XB0 
Go to UniProtKB:  Q91XB0
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ91XB0
Sequence Annotations
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  • Reference Sequence

Find similar nucleic acids by:  Sequence   |   3D Structure  

Entity ID: 1
MoleculeChains LengthOrganismImage
5'-D(*GP*AP*CP*G)-3'A [auth C],
B [auth D]
4N/A
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.10 Å
  • R-Value Free: 0.259 
  • R-Value Work: 0.192 
  • R-Value Observed: 0.195 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 64.85α = 90
b = 57.141β = 107.47
c = 68.47γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
CrystalCleardata collection
d*TREKdata reduction
d*TREKdata scaling
PHASERphasing

Structure Validation

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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2007-02-20
    Type: Initial release
  • Version 1.1: 2008-05-01
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Advisory, Refinement description, Version format compliance
  • Version 1.3: 2023-08-30
    Changes: Data collection, Database references, Derived calculations, Refinement description
  • Version 1.4: 2023-11-15
    Changes: Data collection