2HEL

Crystal structure of a mutant EphA4 kinase domain (Y742A)


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.35 Å
  • R-Value Free: 0.248 
  • R-Value Work: 0.209 

wwPDB Validation   3D Report Full Report


This is version 1.4 of the entry. See complete history


Literature

A change in conformational dynamics underlies the activation of Eph receptor tyrosine kinases.

Wiesner, S.Wybenga-Groot, L.E.Warner, N.Lin, H.Pawson, T.Forman-Kay, J.D.Sicheri, F.

(2006) EMBO J 25: 4686-4696

  • DOI: https://doi.org/10.1038/sj.emboj.7601315
  • Primary Citation of Related Structures:  
    2HEL, 2HEN

  • PubMed Abstract: 

    Eph receptor tyrosine kinases (RTKs) mediate numerous developmental processes. Their activity is regulated by auto-phosphorylation on two tyrosines within the juxtamembrane segment (JMS) immediately N-terminal to the kinase domain (KD). Here, we probe the molecular details of Eph kinase activation through mutational analysis, X-ray crystallography and NMR spectroscopy on auto-inhibited and active EphB2 and EphA4 fragments. We show that a Tyr750Ala gain-of-function mutation in the KD and JMS phosphorylation independently induce disorder of the JMS and its dissociation from the KD. Our X-ray analyses demonstrate that this occurs without major conformational changes to the KD and with only partial ordering of the KD activation segment. However, conformational exchange for helix alphaC in the N-terminal KD lobe and for the activation segment, coupled with increased inter-lobe dynamics, is observed upon kinase activation in our NMR analyses. Overall, our results suggest that a change in inter-lobe dynamics and the sampling of catalytically competent conformations for helix alphaC and the activation segment rather than a transition to a static active conformation underlies Eph RTK activation.


  • Organizational Affiliation

    Structural Biology and Biochemistry, Hospital for Sick Children, Toronto, Ontario, Canada.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Eph receptor A4306Mus musculusMutation(s): 3 
Gene Names: Epha4
UniProt
Find proteins for Q03137 (Mus musculus)
Explore Q03137 
Go to UniProtKB:  Q03137
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ03137
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.35 Å
  • R-Value Free: 0.248 
  • R-Value Work: 0.209 
  • Space Group: P 1 21 1
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 32.283α = 90
b = 101.081β = 108.8
c = 40.95γ = 90
Software Package:
Software NamePurpose
CNSrefinement
DENZOdata reduction
SCALEPACKdata scaling
CNSphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2007-02-13
    Type: Initial release
  • Version 1.1: 2008-05-01
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2021-10-20
    Changes: Database references
  • Version 1.4: 2024-02-14
    Changes: Data collection