2GS2

Crystal Structure of the active EGFR kinase domain


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.80 Å
  • R-Value Free: 0.250 
  • R-Value Work: 0.205 
  • R-Value Observed: 0.248 

Starting Model: experimental
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This is version 1.3 of the entry. See complete history


Literature

An allosteric mechanism for activation of the kinase domain of epidermal growth factor receptor.

Zhang, X.Gureasko, J.Shen, K.Cole, P.A.Kuriyan, J.

(2006) Cell 125: 1137-1149

  • DOI: https://doi.org/10.1016/j.cell.2006.05.013
  • Primary Citation of Related Structures:  
    2GS2, 2GS6, 2GS7

  • PubMed Abstract: 

    The mechanism by which the epidermal growth factor receptor (EGFR) is activated upon dimerization has eluded definition. We find that the EGFR kinase domain can be activated by increasing its local concentration or by mutating a leucine (L834R) in the activation loop, the phosphorylation of which is not required for activation. This suggests that the kinase domain is intrinsically autoinhibited, and an intermolecular interaction promotes its activation. Using further mutational analysis and crystallography we demonstrate that the autoinhibited conformation of the EGFR kinase domain resembles that of Src and cyclin-dependent kinases (CDKs). EGFR activation results from the formation of an asymmetric dimer in which the C-terminal lobe of one kinase domain plays a role analogous to that of cyclin in activated CDK/cyclin complexes. The CDK/cyclin-like complex formed by two kinase domains thus explains the activation of EGFR-family receptors by homo- or heterodimerization.


  • Organizational Affiliation

    Department of Molecular and Cell Biology, Howard Hughes Medical Institute, University of California, Berkeley, 94720, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Epidermal growth factor receptor330Homo sapiensMutation(s): 0 
Gene Names: EGFR
EC: 2.7.10.1
UniProt & NIH Common Fund Data Resources
Find proteins for P00533 (Homo sapiens)
Explore P00533 
Go to UniProtKB:  P00533
PHAROS:  P00533
GTEx:  ENSG00000146648 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP00533
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.80 Å
  • R-Value Free: 0.250 
  • R-Value Work: 0.205 
  • R-Value Observed: 0.248 
  • Space Group: I 2 3
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 145.543α = 90
b = 145.543β = 90
c = 145.543γ = 90
Software Package:
Software NamePurpose
CNSrefinement
PDB_EXTRACTdata extraction
Blu-Icedata collection
HKL-2000data scaling
PHASERphasing

Structure Validation

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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2006-06-20
    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: 2023-08-30
    Changes: Data collection, Database references, Refinement description