1RQQ

Crystal Structure of the Insulin Receptor Kinase in Complex with the SH2 Domain of APS


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.60 Å
  • R-Value Free: 0.277 
  • R-Value Work: 0.229 
  • R-Value Observed: 0.229 

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Ligand Structure Quality Assessment 


This is version 1.5 of the entry. See complete history


Literature

Structural basis for recruitment of the adaptor protein APS to the activated insulin receptor.

Hu, J.Liu, J.Ghirlando, R.Saltiel, A.R.Hubbard, S.R.

(2003) Mol Cell 12: 1379-1389

  • DOI: https://doi.org/10.1016/s1097-2765(03)00487-8
  • Primary Citation of Related Structures:  
    1RPY, 1RQQ

  • PubMed Abstract: 

    The adaptor protein APS is a substrate of the insulin receptor and couples receptor activation with phosphorylation of Cbl to facilitate glucose uptake. The interaction with the activated insulin receptor is mediated by the Src homology 2 (SH2) domain of APS. Here, we present the crystal structure of the APS SH2 domain in complex with the phosphorylated tyrosine kinase domain of the insulin receptor. The structure reveals a novel dimeric configuration of the APS SH2 domain, wherein the C-terminal half of each protomer is structurally divergent from conventional, monomeric SH2 domains. The APS SH2 dimer engages two kinase molecules, with pTyr-1158 of the kinase activation loop bound in the canonical phosphotyrosine binding pocket of the SH2 domain and a second phosphotyrosine, pTyr-1162, coordinated by two lysine residues in beta strand D. This structure provides a molecular visualization of one of the initial downstream recruitment events following insulin activation of its dimeric receptor.


  • Organizational Affiliation

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


Macromolecules
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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Insulin receptor
A, B
306Homo sapiensMutation(s): 5 
Gene Names: INSR
EC: 2.7.1.112
UniProt & NIH Common Fund Data Resources
Find proteins for P06213 (Homo sapiens)
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Go to UniProtKB:  P06213
PHAROS:  P06213
GTEx:  ENSG00000171105 
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UniProt GroupP06213
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  • Reference Sequence
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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
adaptor protein APS
C, D
114Rattus norvegicusMutation(s): 0 
UniProt
Find proteins for Q9Z200 (Rattus norvegicus)
Explore Q9Z200 
Go to UniProtKB:  Q9Z200
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UniProt GroupQ9Z200
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  • Reference Sequence

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Entity ID: 3
MoleculeChains Sequence LengthOrganismDetailsImage
BISUBSTRATE INHIBITOR
E, F
18N/AMutation(s): 0 
Entity Groups  
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Sequence Annotations
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  • Reference Sequence
Small Molecules
Modified Residues  1 Unique
IDChains TypeFormula2D DiagramParent
PTR
Query on PTR
A, B
L-PEPTIDE LINKINGC9 H12 N O6 PTYR
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.60 Å
  • R-Value Free: 0.277 
  • R-Value Work: 0.229 
  • R-Value Observed: 0.229 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 87.216α = 90
b = 96.443β = 90
c = 121.993γ = 90
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
AMoREphasing
CNSrefinement

Structure Validation

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Ligand Structure Quality Assessment 


Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2003-12-30
    Type: Initial release
  • Version 1.1: 2007-10-16
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2021-10-27
    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