2Y8O

Crystal structure of human p38alpha complexed with a MAPK docking peptide


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.95 Å
  • R-Value Free: 0.209 
  • R-Value Work: 0.176 
  • R-Value Observed: 0.177 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Specificity of Linear Motifs that Bind to a Common Mitogen-Activated Protein Kinase Docking Groove.

Garai, A.Zeke, A.Gogl, G.Toro, I.Fordos, F.Blankenburg, H.Barkai, T.Varga, J.Alexa, A.Emig, D.Albrecht, M.Remenyi, A.

(2012) Sci Signal 5: 74

  • DOI: https://doi.org/10.1126/scisignal.2003004
  • Primary Citation of Related Structures:  
    2XRW, 2XS0, 2Y8O, 2Y9Q, 3TEI, 4FMQ

  • PubMed Abstract: 

    Mitogen-activated protein kinases (MAPKs) have a docking groove that interacts with linear "docking" motifs in binding partners. To determine the structural basis of binding specificity between MAPKs and docking motifs, we quantitatively analyzed the ability of 15 docking motifs from diverse MAPK partners to bind to c-Jun amino-terminal kinase 1 (JNK1), p38α, and extracellular signal-regulated kinase 2 (ERK2). Classical docking motifs mediated highly specific binding only to JNK1, and only those motifs with a sequence pattern distinct from the classical MAPK binding docking motif consensus differentiated between the topographically similar docking grooves of ERK and p38α. Crystal structures of four complexes of MAPKs with docking peptides, representing JNK-specific, ERK-specific, or ERK- and p38-selective binding modes, revealed that the regions located between consensus positions in the docking motifs showed conformational diversity. Although the consensus positions in the docking motifs served as anchor points that bound to common MAPK surface features and mostly contributed to docking in a nondiscriminatory fashion, the conformation of the intervening region between the anchor points mostly determined specificity. We designed peptides with tailored MAPK binding profiles by rationally changing the length and amino acid composition of intervening regions located between anchor points. These results suggest a coherent structural model for MAPK docking specificity that reveals how short linear motifs binding to a common kinase docking groove can mediate diverse interaction patterns and contribute to correct MAPK partner selection in signaling networks.


  • Organizational Affiliation

    Department of Biochemistry, Eötvös Loránd University, Pázmány Péter sétány 1/C, 1117 Budapest, Hungary.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
MITOGEN-ACTIVATED PROTEIN KINASE 14362Homo sapiensMutation(s): 1 
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
Expand
  • Reference Sequence

Find similar proteins by:  Sequence   |   3D Structure  

Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
DUAL SPECIFICITY MITOGEN-ACTIVATED PROTEIN KINASE KINASE 614Homo 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: 1.95 Å
  • R-Value Free: 0.209 
  • R-Value Work: 0.176 
  • R-Value Observed: 0.177 
  • Space Group: P 31 2 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 81.92α = 90
b = 81.92β = 90
c = 122.59γ = 120
Software Package:
Software NamePurpose
PHENIXrefinement
XDSdata reduction
XSCALEdata scaling
PHASERphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2012-02-22
    Type: Initial release
  • Version 1.1: 2012-10-24
    Changes: Database references
  • Version 1.2: 2018-03-07
    Changes: Source and taxonomy
  • Version 1.3: 2023-12-20
    Changes: Data collection, Database references, Other, Refinement description