5YDF

Crystal structure of a disease-related gene, hCDC73(1-100)


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.40 Å
  • R-Value Free: 0.174 
  • R-Value Work: 0.135 
  • R-Value Observed: 0.137 

wwPDB Validation   3D Report Full Report


This is version 1.1 of the entry. See complete history


Literature

Crystal structure of the N-terminal domain of human CDC73 and its implications for the hyperparathyroidism-jaw tumor (HPT-JT) syndrome

Sun, W.Kuang, X.L.Liu, Y.P.Tian, L.F.Yan, X.X.Xu, W.

(2017) Sci Rep 7: 15638-15638

  • DOI: https://doi.org/10.1038/s41598-017-15715-9
  • Primary Citation of Related Structures:  
    5YDE, 5YDF

  • PubMed Abstract: 

    CDC73/Parafibromin is a critical component of the Paf1 complex (PAF1C), which is involved in transcriptional elongation and histone modifications. Mutations of the human CDC73/HRPT2 gene are associated with hyperparathyroidism-jaw tumor (HPT-JT) syndrome, an autosomal dominant disorder. CDC73/parafibromin was initially recognized as a tumor suppressor by inhibiting cell proliferation via repression of cyclin D1 and c-myc genes. In recent years, it has also shown oncogenic features by activating the canonical Wnt/β-catenin signal pathway. Here, through limited proteolysis analysis, we demonstrate that the evolutionarily conserved human CDC73 N-terminal 111 residues form a globularly folded domain (hCDC73-NTD). We have determined a crystal structure of hCDC73-NTD at 1.02 Å resolution, which reveals a novel protein fold. CDC73-NTD contains an extended hydrophobic groove on its surface that may be important for its function. Most pathogenic CDC73 missense mutations associated with the HPT-JT syndrome are located in the region encoding CDC73-NTD. Our crystal and biochemical data indicate that most CDC73 missense mutations disrupt the folding of the hydrophobic core of hCDC73-NTD, while others such as the K34Q mutant reduce its thermostability. Overall, our results provide a solid structural basis for understanding the structure and function of CDC73 and its association with the HPT-JT syndrome and other diseases.


  • Organizational Affiliation

    National Laboratory of Biomacromolecules, CAS Center for Excellence in Biomacromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, P. R. China.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Parafibromin
A, B
101Homo sapiensMutation(s): 0 
Gene Names: CDC73C1orf28HRPT2
UniProt & NIH Common Fund Data Resources
Find proteins for Q6P1J9 (Homo sapiens)
Explore Q6P1J9 
Go to UniProtKB:  Q6P1J9
PHAROS:  Q6P1J9
GTEx:  ENSG00000134371 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ6P1J9
Sequence Annotations
Expand
  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.40 Å
  • R-Value Free: 0.174 
  • R-Value Work: 0.135 
  • R-Value Observed: 0.137 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 28.59α = 90
b = 53.504β = 95.66
c = 65.734γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
HKL-3000data reduction
HKL-3000data scaling
PHENIXphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2017-12-20
    Type: Initial release
  • Version 1.1: 2024-03-27
    Changes: Data collection, Database references