4GT4

Structure of unliganded, inactive Ror2 kinase domain


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.41 Å
  • R-Value Free: 0.205 
  • R-Value Work: 0.177 
  • R-Value Observed: 0.179 

wwPDB Validation   3D Report Full Report


This is version 1.2 of the entry. See complete history


Literature

Assessing the range of kinase autoinhibition mechanisms in the insulin receptor family.

Artim, S.C.Mendrola, J.M.Lemmon, M.A.

(2012) Biochem J 448: 213-220

  • DOI: https://doi.org/10.1042/BJ20121365
  • Primary Citation of Related Structures:  
    4GT4, 4GT5

  • PubMed Abstract: 

    To investigate the range of autoinhibitory mechanisms used by TKDs (tyrosine kinase domains) from the insulin receptor family of RTKs (receptor tyrosine kinases), we determined crystal structures of TKDs from TrkA (tropomyosin receptor kinase A, a nerve growth factor receptor) and Ror2 (receptor tyrosine kinase-like orphan receptor 2, an unconventional Wnt receptor). TrkA autoinhibition closely resembles that seen for the insulin receptor, relying on projection of an activation loop tyrosine residue into the substrate-binding site and occlusion of the ATP-binding site by the activation loop. Ror2 employs similar mechanisms, but the unusual replacement of the phenylalanine residue in its Asp-Phe-Gly motif with leucine necessitates occlusion of the ATP-binding site by other means. The unusual Asp-Leu-Gly motif in Ror2 is displaced compared with other inactive kinases, allowing the activation loop to interact directly with the TKD's αC helix, in another mode of autoinhibition that is characteristic of the other extreme of this receptor family: ALK (anaplastic lymphoma kinase) and Met. These findings provide insight into the expected range of activating mutations in these TKDs in cancer. We also describe symmetrical dimers of the inactive TrkA TKD resembling those found in other RTKs, possibly reflecting an arrangement of kinase domains in a pre-formed TrkA dimer.


  • Organizational Affiliation

    Department of Biochemistry and Biophysics, University of Pennsylvania Perelman School of Medicine, 809C Stellar-Chance Laboratories, 422 Curie Boulevard, Philadelphia, PA 19104, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Tyrosine-protein kinase transmembrane receptor ROR2
A, B
308Homo sapiensMutation(s): 0 
Gene Names: NTRKR2ROR2
EC: 2.7.10.1
UniProt & NIH Common Fund Data Resources
Find proteins for Q01974 (Homo sapiens)
Explore Q01974 
Go to UniProtKB:  Q01974
PHAROS:  Q01974
GTEx:  ENSG00000169071 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ01974
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.41 Å
  • R-Value Free: 0.205 
  • R-Value Work: 0.177 
  • R-Value Observed: 0.179 
  • Space Group: C 2 2 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 102.834α = 90
b = 112.918β = 90
c = 114.759γ = 90
Software Package:
Software NamePurpose
HKL-2000data collection
PHASERphasing
PHENIXrefinement
HKL-2000data reduction
HKL-2000data scaling

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2012-09-26
    Type: Initial release
  • Version 1.1: 2012-10-03
    Changes: Database references
  • Version 1.2: 2012-11-21
    Changes: Database references