2H5K

Crystal Structure of Complex Between the Domain-Swapped Dimeric Grb2 SH2 Domain and Shc-Derived Ligand, Ac-NH-pTyr-Val-Asn-NH2


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.25 Å
  • R-Value Free: 0.300 
  • R-Value Work: 0.247 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Structural and energetic aspects of Grb2-SH2 domain-swapping.

Benfield, A.P.Whiddon, B.B.Clements, J.H.Martin, S.F.

(2007) Arch Biochem Biophys 462: 47-53

  • DOI: https://doi.org/10.1016/j.abb.2007.03.010
  • Primary Citation of Related Structures:  
    2H46, 2H5K

  • PubMed Abstract: 

    The SH2 domain of growth factor receptor-bound protein 2 (Grb2) has been the focus of numerous studies, primarily because of the important roles it plays in signal transduction. More recently, it has emerged as a useful protein to study the consequences of ligand preorganization upon energetics and structure in protein-ligand interactions. The Grb2-SH2 domain is known to form a domain-swapped dimer, and as part of our investigations toward correlating structure and energetics in biological systems, we examined the effects that domain-swapping dimerization of the Grb2-SH2 domain had upon ligand binding affinities. Isothermal titration calorimetry was performed using Grb2-SH2 in both its monomeric and domain-swapped dimeric forms and a phosphorylated tripeptide AcNH-pTyr-Val-Asn-NH(2) that is similar to the Shc sequence recognized by Grb2-SH2 in vivo. The two binding sites of domain-swapped dimer exhibited a 4- and a 13-fold reduction in ligand affinity compared to monomer. Crystal structures of peptide-bound and uncomplexed forms of Grb2-SH2 domain-swapped dimer were obtained and reveal that the orientation of residues V122, V123, and R142 may influence the conformation of W121, an amino acid that is believed to play an important role in Grb2-SH2 ligand sequence specificity. These findings suggest that domain-swapping of Grb2-SH2 not only results in a lower affinity for a Shc-derived ligand, but it may also affect ligand specificity.


  • Organizational Affiliation

    Department of Chemistry and Biochemistry, University of Texas, Austin, TX 78712, USA.


Macromolecules
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Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
Growth factor receptor-bound protein 2
A, B
116Homo sapiensMutation(s): 0 
Gene Names: GRB2ASH
UniProt & NIH Common Fund Data Resources
Find proteins for P62993 (Homo sapiens)
Explore P62993 
Go to UniProtKB:  P62993
PHAROS:  P62993
GTEx:  ENSG00000177885 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP62993
Sequence Annotations
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  • Reference Sequence

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Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Shc-Derived Ligand5N/AMutation(s): 0 
Sequence Annotations
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  • Reference Sequence
Small Molecules
Ligands 1 Unique
IDChains Name / Formula / InChI Key2D Diagram3D Interactions
CAC
Query on CAC

Download Ideal Coordinates CCD File 
D [auth B]CACODYLATE ION
C2 H6 As O2
OGGXGZAMXPVRFZ-UHFFFAOYSA-M
Modified Residues  1 Unique
IDChains TypeFormula2D DiagramParent
PTR
Query on PTR
C
L-PEPTIDE LINKINGC9 H12 N O6 PTYR
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 3.25 Å
  • R-Value Free: 0.300 
  • R-Value Work: 0.247 
  • Space Group: P 62 2 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 94.859α = 90
b = 94.859β = 90
c = 139.236γ = 120
Software Package:
Software NamePurpose
DENZOdata reduction
SCALEPACKdata scaling
MOLREPphasing
CNSrefinement
PDB_EXTRACTdata extraction
CrystalCleardata reduction

Structure Validation

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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2006-08-15
    Type: Initial release
  • Version 1.1: 2008-05-01
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Non-polymer description, Version format compliance
  • Version 1.3: 2017-10-18
    Changes: Refinement description