6HKS

Crystal structure of the PTPN3 PDZ domain bound to the HPV16 E6 oncoprotein C-terminal peptide


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.19 Å
  • R-Value Free: 0.247 
  • R-Value Work: 0.194 
  • R-Value Observed: 0.197 

wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

Structural and functional characterization of the PDZ domain of the human phosphatase PTPN3 and its interaction with the human papillomavirus E6 oncoprotein.

Genera, M.Samson, D.Raynal, B.Haouz, A.Baron, B.Simenel, C.Guerois, R.Wolff, N.Caillet-Saguy, C.

(2019) Sci Rep 9: 7438-7438

  • DOI: https://doi.org/10.1038/s41598-019-43932-x
  • Primary Citation of Related Structures:  
    6HKS

  • PubMed Abstract: 

    The human protein tyrosine phosphatase non-receptor type 3 (PTPN3) is a PDZ (PSD-95/Dlg/ZO-1) domain-containing phosphatase with a tumor-suppressive or a tumor-promoting role in many cancers. Interestingly, the high-risk genital human papillomavirus (HPV) types 16 and 18 target the PDZ domain of PTPN3. The presence of a PDZ binding motif (PBM) on E6 confers interaction with a number of different cellular PDZ domain-containing proteins and is a marker of high oncogenic potential. Here, we report the molecular basis of interaction between the PDZ domain of PTPN3 and the PBM of the HPV E6 protein. We combined biophysical, NMR and X-ray experiments to investigate the structural and functional properties of the PDZ domain of PTPN3. We showed that the C-terminal sequences from viral proteins encompassing a PBM interact with PTPN3-PDZ with similar affinities to the endogenous PTPN3 ligand MAP kinase p38γ. PBM binding stabilizes the PDZ domain of PTPN3. We solved the X-ray structure of the PDZ domain of PTPN3 in complex with the PBM of the HPV E6 protein. The crystal structure and the NMR chemical shift mapping of the PTPN3-PDZ/peptide complex allowed us to pinpoint the main structural determinants of recognition of the C-terminal sequence of the E6 protein and the long-range perturbations induced upon PBM binding.


  • Organizational Affiliation

    Récepteurs-Canaux, Institut Pasteur, UMR 3571, CNRS, F-75724, Paris, France.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Tyrosine-protein phosphatase non-receptor type 3
A, B, C, D, E
A, B, C, D, E, F
114Homo sapiensMutation(s): 0 
Gene Names: PTPN3PTPH1
EC: 3.1.3.48
UniProt & NIH Common Fund Data Resources
Find proteins for P26045 (Homo sapiens)
Explore P26045 
Go to UniProtKB:  P26045
PHAROS:  P26045
GTEx:  ENSG00000070159 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP26045
Sequence Annotations
Expand
  • Reference Sequence

Find similar proteins by:  Sequence   |   3D Structure  

Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Protein E6
G, H, I, J, K
G, H, I, J, K, L
11Human papillomavirus 16Mutation(s): 0 
Gene Names: E6
UniProt
Find proteins for P03126 (Human papillomavirus type 16)
Explore P03126 
Go to UniProtKB:  P03126
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP03126
Sequence Annotations
Expand
  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.19 Å
  • R-Value Free: 0.247 
  • R-Value Work: 0.194 
  • R-Value Observed: 0.197 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 46.62α = 90
b = 77.43β = 90.14
c = 130.03γ = 90
Software Package:
Software NamePurpose
PHENIXrefinement
XDSdata reduction
Aimlessdata scaling
PHASERphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2019-05-22
    Type: Initial release
  • Version 1.1: 2019-05-29
    Changes: Data collection, Database references
  • Version 1.2: 2024-01-17
    Changes: Data collection, Database references, Refinement description