2HDX

Crystal structure of the Src homology-2 domain of SH2-B in complex with Jak2 pTyr813 phosphopeptide


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.35 Å
  • R-Value Free: 0.240 
  • R-Value Work: 0.210 
  • R-Value Observed: 0.240 

wwPDB Validation   3D Report Full Report


This is version 1.5 of the entry. See complete history


Literature

Structural Basis for Phosphotyrosine Recognition by the Src Homology-2 Domains of the Adapter Proteins SH2-B and APS.

Hu, J.Hubbard, S.R.

(2006) J Mol Biol 361: 69-79

  • DOI: https://doi.org/10.1016/j.jmb.2006.05.070
  • Primary Citation of Related Structures:  
    2HDV, 2HDX

  • PubMed Abstract: 

    SH2-B, APS, and Lnk constitute a family of adapter proteins that modulate signaling by protein tyrosine kinases. These adapters contain an N-terminal dimerization region, a pleckstrin homology domain, and a C-terminal Src homology-2 (SH2) domain. SH2-B is recruited via its SH2 domain to various protein tyrosine kinases, including Janus kinase-2 (Jak2) and the insulin receptor. Here, we present the crystal structure at 2.35 A resolution of the SH2 domain of SH2-B in complex with a phosphopeptide representing the SH2-B recruitment site in Jak2 (pTyr813). The structure reveals a canonical SH2 domain-phosphopeptide binding mode, but with specific recognition of a glutamate at the +1 position relative to phosphotyrosine, in addition to recognition of a hydrophobic residue at the +3 position. Biochemical studies of SH2-B and APS demonstrate that, although the SH2 domains of these two adapter proteins share 79% sequence identity, the SH2-B SH2 domain binds preferentially to Jak2, whereas the APS SH2 domain has higher affinity for the insulin receptor. This differential specificity is attributable to the difference in the oligomeric states of the two SH2 domains: monomeric for SH2-B and dimeric for APS.


  • Organizational Affiliation

    Structural Biology Program, Skirball Institute of Biomolecular Medicine, and Department of Pharmacology, New York University School of Medicine, NY 10016, USA. hubbard@saturn.med.nyu.edu


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
SH2-B PH domain containing signaling mediator 1 gamma isoform
A, B, C, D, E
A, B, C, D, E, F
111Mus musculusMutation(s): 3 
Gene Names: Sh2bpsm1
UniProt & NIH Common Fund Data Resources
Find proteins for Q91ZM2 (Mus musculus)
Explore Q91ZM2 
Go to UniProtKB:  Q91ZM2
IMPC:  MGI:1201407
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ91ZM2
Sequence Annotations
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  • Reference Sequence

Find similar proteins by:  Sequence   |   3D Structure  

Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Jak2 protein
G, H, I, J, K
G, H, I, J, K, L
11N/AMutation(s): 1 
UniProt
Find proteins for Q62120 (Mus musculus)
Explore Q62120 
Go to UniProtKB:  Q62120
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ62120
Sequence Annotations
Expand
  • Reference Sequence
Small Molecules
Modified Residues  1 Unique
IDChains TypeFormula2D DiagramParent
PTR
Query on PTR
G, H, I, J, K
G, H, I, J, K, L
L-PEPTIDE LINKINGC9 H12 N O6 PTYR
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.35 Å
  • R-Value Free: 0.240 
  • R-Value Work: 0.210 
  • R-Value Observed: 0.240 
  • Space Group: P 21 21 21
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 44.21α = 90
b = 74.19β = 90
c = 239.22γ = 90
Software Package:
Software NamePurpose
AMoREphasing
CNSrefinement

Structure Validation

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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2006-08-08
    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: 2023-08-30
    Changes: Data collection, Refinement description
  • Version 1.5: 2023-11-15
    Changes: Data collection