2J0M

Crystal structure a two-chain complex between the FERM and kinase domains of focal adhesion kinase.


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.80 Å
  • R-Value Free: 0.282 
  • R-Value Work: 0.221 
  • R-Value Observed: 0.224 

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Ligand Structure Quality Assessment 


This is version 1.5 of the entry. See complete history


Literature

Structural Basis for the Autoinhibition of Focal Adhesion Kinase.

Lietha, D.Cai, X.Li, Y.Schaller, M.D.Eck, M.J.

(2007) Cell 129: 1177

  • DOI: https://doi.org/10.1016/j.cell.2007.05.041
  • Primary Citation of Related Structures:  
    2J0J, 2J0K, 2J0L, 2J0M

  • PubMed Abstract: 

    Appropriate tyrosine kinase signaling depends on coordinated sequential coupling of protein-protein interactions with catalytic activation. Focal adhesion kinase (FAK) integrates signals from integrin and growth factor receptors to regulate cellular responses including cell adhesion, migration, and survival. Here, we describe crystal structures representing both autoinhibited and active states of FAK. The inactive structure reveals a mechanism of inhibition in which the N-terminal FERM domain directly binds the kinase domain, blocking access to the catalytic cleft and protecting the FAK activation loop from Src phosphorylation. Additionally, the FERM domain sequesters the Tyr397 autophosphorylation and Src recruitment site, which lies in the linker connecting the FERM and kinase domains. The active phosphorylated FAK kinase adopts a conformation that is immune to FERM inhibition. Our biochemical and structural analysis shows how the architecture of autoinhibited FAK orchestrates an activation sequence of FERM domain displacement, linker autophosphorylation, Src recruitment, and full catalytic activation.


  • Organizational Affiliation

    Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA 02115, USA.


Macromolecules
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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
FOCAL ADHESION KINASE 1371Gallus gallusMutation(s): 0 
EC: 2.7.10.2
UniProt
Find proteins for Q00944 (Gallus gallus)
Explore Q00944 
Go to UniProtKB:  Q00944
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ00944
Sequence Annotations
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  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
FOCAL ADHESION KINASE 1276Gallus gallusMutation(s): 0 
EC: 2.7.10.2
UniProt
Find proteins for Q00944 (Gallus gallus)
Explore Q00944 
Go to UniProtKB:  Q00944
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ00944
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
4ST
Query on 4ST

Download Ideal Coordinates CCD File 
C [auth B]1,2,3,4-TETRAHYDROGEN-STAUROSPORINE
C28 H30 N4 O3
KIZWKTROWIIMNN-FYTWVXJKSA-N
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.80 Å
  • R-Value Free: 0.282 
  • R-Value Work: 0.221 
  • R-Value Observed: 0.224 
  • Space Group: C 2 2 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 67.49α = 90
b = 90.6β = 90
c = 242.61γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
XDSdata reduction
XDSdata scaling
PHASERphasing

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2007-07-03
    Type: Initial release
  • Version 1.1: 2011-07-13
    Changes: Advisory, Refinement description, Version format compliance
  • Version 1.2: 2013-12-04
    Changes: Non-polymer description, Source and taxonomy
  • Version 1.3: 2018-01-17
    Changes: Advisory, Structure summary
  • Version 1.4: 2019-04-03
    Changes: Data collection, Source and taxonomy
  • Version 1.5: 2023-12-13
    Changes: Advisory, Data collection, Database references, Derived calculations, Other, Refinement description