2AUH

Crystal structure of the Grb14 BPS region in complex with the insulin receptor tyrosine kinase


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.20 Å
  • R-Value Free: 0.254 
  • R-Value Work: 0.223 
  • R-Value Observed: 0.223 

wwPDB Validation   3D Report Full Report


This is version 1.5 of the entry. See complete history


Literature

Structural basis for inhibition of the insulin receptor by the adaptor protein grb14.

Depetris, R.S.Hu, J.Gimpelevich, I.Holt, L.J.Daly, R.J.Hubbard, S.R.

(2005) Mol Cell 20: 325-333

  • DOI: https://doi.org/10.1016/j.molcel.2005.09.001
  • Primary Citation of Related Structures:  
    2AUG, 2AUH

  • PubMed Abstract: 

    Grb14, a member of the Grb7 adaptor protein family, possesses a pleckstrin homology (PH) domain, a C-terminal Src homology-2 (SH2) domain, and an intervening stretch of approximately 45 residues known as the BPS region, which is unique to this adaptor family. Previous studies have demonstrated that Grb14 is a tissue-specific negative regulator of insulin receptor signaling and that inhibition is mediated by the BPS region. We have determined the crystal structure of the Grb14 BPS region in complex with the tyrosine kinase domain of the insulin receptor. The structure reveals that the N-terminal portion of the BPS region binds as a pseudosubstrate inhibitor in the substrate peptide binding groove of the kinase. Together with the crystal structure of the SH2 domain, we present a model for the interaction of Grb14 with the insulin receptor, which indicates how Grb14 functions as a selective protein inhibitor of insulin signaling.


  • Organizational Affiliation

    Structural Biology Program, Skirball Institute of Biomolecular Medicine and Department of Pharmacology, New York University School of Medicine, New York, New York 10016, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Insulin receptor306Homo sapiensMutation(s): 5 
Gene Names: INSR
EC: 2.7.1.112
UniProt & NIH Common Fund Data Resources
Find proteins for P06213 (Homo sapiens)
Explore P06213 
Go to UniProtKB:  P06213
PHAROS:  P06213
GTEx:  ENSG00000171105 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP06213
Sequence Annotations
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  • Reference Sequence
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Growth factor receptor-bound protein 1459Homo sapiensMutation(s): 1 
Gene Names: GRB14
UniProt & NIH Common Fund Data Resources
Find proteins for Q14449 (Homo sapiens)
Explore Q14449 
Go to UniProtKB:  Q14449
PHAROS:  Q14449
GTEx:  ENSG00000115290 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ14449
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Modified Residues  1 Unique
IDChains TypeFormula2D DiagramParent
PTR
Query on PTR
A
L-PEPTIDE LINKINGC9 H12 N O6 PTYR
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.20 Å
  • R-Value Free: 0.254 
  • R-Value Work: 0.223 
  • R-Value Observed: 0.223 
  • Space Group: P 62
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 127.182α = 90
b = 127.182β = 90
c = 65.925γ = 120
Software Package:
Software NamePurpose
CNSrefinement
HKL-2000data reduction
HKL-2000data scaling
AMoREphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2005-11-01
    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, Derived calculations
  • Version 1.4: 2023-08-23
    Changes: Data collection, Refinement description
  • Version 1.5: 2023-11-15
    Changes: Data collection