2WH0

Recognition of an intrachain tandem 14-3-3 binding site within protein kinase C epsilon


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.25 Å
  • R-Value Free: 0.235 
  • R-Value Work: 0.181 
  • R-Value Observed: 0.183 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Recognition of an Intra-Chain Tandem 14-3-3 Binding Site within Pkc Epsilon.

Kostelecky, B.Saurin, A.T.Purkiss, A.Parker, P.J.Mcdonald, N.Q.

(2009) EMBO Rep 10: 983

  • DOI: https://doi.org/10.1038/embor.2009.150
  • Primary Citation of Related Structures:  
    2WH0

  • PubMed Abstract: 

    The phosphoserine/threonine binding protein 14-3-3 stimulates the catalytic activity of protein kinase C-epsilon (PKCepsilon) by engaging two tandem phosphoserine-containing motifs located between the PKCepsilon regulatory and catalytic domains (V3 region). Interaction between 14-3-3 and this region of PKCepsilon is essential for the completion of cytokinesis. Here, we report the crystal structure of 14-3-3zeta bound to a synthetic diphosphorylated PKCepsilon V3 region revealing how a consensus 14-3-3 site and a divergent 14-3-3 site cooperate to bind to 14-3-3 and so activate PKCepsilon. Thermodynamic data show a markedly enhanced binding affinity for two-site phosphopeptides over single-site 14-3-3 binding motifs and identifies Ser 368 as a gatekeeper phosphorylation site in this physiologically relevant 14-3-3 ligand. This dual-site intra-chain recognition has implications for other 14-3-3 targets, which seem to have only a single 14-3-3 motif, as other lower affinity and cryptic 14-3-3 gatekeeper sites might exist.


  • Organizational Affiliation

    Structural Biology Laboratory, London Research Institute, Cancer Research UK, 44 Lincoln's Inn Fields, London WC2A 3PX, UK.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
14-3-3 PROTEIN ZETA/DELTA
A, B, C, D
245Homo sapiensMutation(s): 0 
UniProt & NIH Common Fund Data Resources
Find proteins for P63104 (Homo sapiens)
Explore P63104 
Go to UniProtKB:  P63104
PHAROS:  P63104
GTEx:  ENSG00000164924 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP63104
Sequence Annotations
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  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
PROTEIN KINASE C EPSILON TYPE, NPKC-EPSILONE [auth Q],
F [auth R]
31Homo sapiensMutation(s): 0 
EC: 2.7.11.13
UniProt & NIH Common Fund Data Resources
Find proteins for Q02156 (Homo sapiens)
Explore Q02156 
Go to UniProtKB:  Q02156
PHAROS:  Q02156
GTEx:  ENSG00000171132 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ02156
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Modified Residues  1 Unique
IDChains TypeFormula2D DiagramParent
SEP
Query on SEP
E [auth Q],
F [auth R]
L-PEPTIDE LINKINGC3 H8 N O6 PSER
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.25 Å
  • R-Value Free: 0.235 
  • R-Value Work: 0.181 
  • R-Value Observed: 0.183 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 71.13α = 90
b = 78.16β = 90.1
c = 108.52γ = 90
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: 2009-08-18
    Type: Initial release
  • Version 1.1: 2011-05-08
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2023-12-13
    Changes: Data collection, Database references, Derived calculations, Other, Refinement description