5ETF

Structure of dead kinase MAPK14 with bound the KIM domain of MKK6


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.40 Å
  • R-Value Free: 0.231 
  • R-Value Work: 0.163 
  • R-Value Observed: 0.166 

wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

Structural Basis for the Subversion of MAP Kinase Signaling by an Intrinsically Disordered Parasite Secreted Agonist.

Pellegrini, E.Palencia, A.Braun, L.Kapp, U.Bougdour, A.Belrhali, H.Bowler, M.W.Hakimi, M.A.

(2017) Structure 25: 16-26

  • DOI: https://doi.org/10.1016/j.str.2016.10.011
  • Primary Citation of Related Structures:  
    5ETA, 5ETF

  • PubMed Abstract: 

    The causative agent of toxoplasmosis, the intracellular parasite Toxoplasma gondii, delivers a protein, GRA24, into the cells it infects that interacts with the mitogen-activated protein (MAP) kinase p38α (MAPK14), leading to activation and nuclear translocation of the host kinase and a subsequent inflammatory response that controls the progress of the parasite. The purification of a recombinant complex of GRA24 and human p38α has allowed the molecular basis of this activation to be determined. GRA24 is shown to be intrinsically disordered, binding two kinases that act independently, and is the only factor required to bypass the canonical mitogen-activated protein kinase activation pathway. An adapted kinase interaction motif (KIM) forms a highly stable complex that competes with cytoplasmic regulatory partners. In addition, the recombinant complex forms a powerful in vitro tool to evaluate the specificity and effectiveness of p38α inhibitors that have advanced to clinical trials, as it provides a hitherto unavailable stable and highly active form of p38α.


  • Organizational Affiliation

    European Molecular Biology Laboratory, Grenoble Outstation, 71 Avenue des Martyrs, CS 90181, 38042 Grenoble, France; Unit for Virus Host Cell Interactions, Université Grenoble Alpes-EMBL-CNRS, 71 Avenue des Martyrs, CS 90181, 38042 Grenoble, France.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Mitogen-activated protein kinase 14360Homo sapiensMutation(s): 0 
Gene Names: MAPK14CSBPCSBP1CSBP2CSPB1MXI2SAPK2A
EC: 2.7.11.24
UniProt & NIH Common Fund Data Resources
Find proteins for Q16539 (Homo sapiens)
Explore Q16539 
Go to UniProtKB:  Q16539
PHAROS:  Q16539
GTEx:  ENSG00000112062 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ16539
Sequence Annotations
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  • Reference Sequence

Find similar proteins by:  Sequence   |   3D Structure  

Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Dual specificity mitogen-activated protein kinase kinase 615Homo sapiensMutation(s): 0 
EC: 2.7.12.2
UniProt & NIH Common Fund Data Resources
Find proteins for P52564 (Homo sapiens)
Explore P52564 
Go to UniProtKB:  P52564
PHAROS:  P52564
GTEx:  ENSG00000108984 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP52564
Sequence Annotations
Expand
  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.40 Å
  • R-Value Free: 0.231 
  • R-Value Work: 0.163 
  • R-Value Observed: 0.166 
  • Space Group: P 31 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 82.383α = 90
b = 82.383β = 90
c = 123.335γ = 120
Software Package:
Software NamePurpose
PHENIXrefinement
XDSdata reduction
Aimlessdata scaling
MOLREPphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2016-10-26
    Type: Initial release
  • Version 1.1: 2016-12-07
    Changes: Database references
  • Version 1.2: 2017-01-18
    Changes: Database references