3OMH

Crystal structure of PTPN22 in complex with SKAP-HOM pTyr75 peptide


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.90 Å
  • R-Value Free: 0.260 
  • R-Value Work: 0.229 
  • R-Value Observed: 0.231 

wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

Substrate Specificity of Lymphoid-specific Tyrosine Phosphatase (Lyp) and Identification of Src Kinase-associated Protein of 55 kDa Homolog (SKAP-HOM) as a Lyp Substrate.

Yu, X.Chen, M.Zhang, S.Yu, Z.H.Sun, J.P.Wang, L.Liu, S.Imasaki, T.Takagi, Y.Zhang, Z.Y.

(2011) J Biol Chem 286: 30526-30534

  • DOI: https://doi.org/10.1074/jbc.M111.254722
  • Primary Citation of Related Structures:  
    3OMH

  • PubMed Abstract: 

    A missense single-nucleotide polymorphism in the gene encoding the lymphoid-specific tyrosine phosphatase (Lyp) has been identified as a causal factor in a wide spectrum of autoimmune diseases. Interestingly, the autoimmune-predisposing variant of Lyp appears to represent a gain-of-function mutation, implicating Lyp as an attractive target for the development of effective strategies for the treatment of many autoimmune disorders. Unfortunately, the precise biological functions of Lyp in signaling cascades and cellular physiology are poorly understood. Identification and characterization of Lyp substrates will help define the chain of molecular events coupling Lyp dysfunction to diseases. In the current study, we identified consensus sequence motifs for Lyp substrate recognition using an "inverse alanine scanning" combinatorial library approach. The intrinsic sequence specificity data led to the discovery and characterization of SKAP-HOM, a cytosolic adaptor protein required for proper activation of the immune system, as a bona fide Lyp substrate. To determine the molecular basis for Lyp substrate recognition, we solved crystal structures of Lyp in complex with the consensus peptide as well as the phosphopeptide derived from SKAP-HOM. Together with the biochemical data, the structures define the molecular determinants for Lyp substrate specificity and provide a solid foundation upon which novel therapeutics targeting Lyp can be developed for multiple autoimmune diseases.


  • Organizational Affiliation

    Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, Indiana 46202.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Tyrosine-protein phosphatase non-receptor type 22
A, B, C, D
313Homo sapiensMutation(s): 1 
Gene Names: PTPN22PTPN8
EC: 3.1.3.48
UniProt & NIH Common Fund Data Resources
Find proteins for Q9Y2R2 (Homo sapiens)
Explore Q9Y2R2 
Go to UniProtKB:  Q9Y2R2
PHAROS:  Q9Y2R2
GTEx:  ENSG00000134242 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ9Y2R2
Sequence Annotations
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  • Reference Sequence

Find similar proteins by:  Sequence   |   3D Structure  

Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Src kinase-associated phosphoprotein 2
E, F, G, H
9Homo sapiensMutation(s): 0 
UniProt & NIH Common Fund Data Resources
Find proteins for O75563 (Homo sapiens)
Explore O75563 
Go to UniProtKB:  O75563
PHAROS:  O75563
GTEx:  ENSG00000005020 
Entity Groups  
UniProt GroupO75563
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Modified Residues  1 Unique
IDChains TypeFormula2D DiagramParent
PTR
Query on PTR
E, F, G, H
L-PEPTIDE LINKINGC9 H12 N O6 PTYR
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.90 Å
  • R-Value Free: 0.260 
  • R-Value Work: 0.229 
  • R-Value Observed: 0.231 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 115.229α = 90
b = 46.707β = 101.43
c = 121.493γ = 90
Software Package:
Software NamePurpose
HKL-3000data collection
PHASESphasing
CNSrefinement
HKL-3000data reduction
HKL-3000data scaling

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2011-06-29
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Version format compliance
  • Version 1.2: 2011-09-14
    Changes: Database references