1FYR

DIMER FORMATION THROUGH DOMAIN SWAPPING IN THE CRYSTAL STRUCTURE OF THE GRB2-SH2 AC-PYVNV COMPLEX


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.40 Å
  • R-Value Free: 0.270 
  • R-Value Work: 0.217 
  • R-Value Observed: 0.220 

wwPDB Validation   3D Report Full Report


This is version 1.4 of the entry. See complete history


Literature

Dimer formation through domain swapping in the crystal structure of the Grb2-SH2-Ac-pYVNV complex.

Schiering, N.Casale, E.Caccia, P.Giordano, P.Battistini, C.

(2000) Biochemistry 39: 13376-13382

  • DOI: https://doi.org/10.1021/bi0012336
  • Primary Citation of Related Structures:  
    1FYR

  • PubMed Abstract: 

    Src homology 2 (SH2) domains are key modules in intracellular signal transduction. They link activated cell surface receptors to downstream targets by binding to phosphotyrosine-containing sequence motifs. The crystal structure of a Grb2-SH2 domain-phosphopeptide complex was determined at 2.4 A resolution. The asymmetric unit contains four polypeptide chains. There is an unexpected domain swap so that individual chains do not adopt a closed SH2 fold. Instead, reorganization of the EF loop leads to an open, nonglobular fold, which associates with an equivalent partner to generate an intertwined dimer. As in previously reported crystal structures of canonical Grb2-SH2 domain-peptide complexes, each of the four hybrid SH2 domains in the two domain-swapped dimers binds the phosphopeptide in a type I beta-turn conformation. This report is the first to describe domain swapping for an SH2 domain. While in vivo evidence of dimerization of Grb2 exists, our SH2 dimer is metastable and a physiological role of this new form of dimer formation remains to be demonstrated.


  • Organizational Affiliation

    Department of Structural Chemistry, Discovery Research Oncology, Viale Pasteur 10, 20014 Nerviano (MI), Italy. nikolaus.schiering@eu.pnu.com


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
GROWTH FACTOR RECEPTOR-BOUND PROTEIN 2
A, B, C, D
114Homo sapiensMutation(s): 0 
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
HEPATOCYTE GROWTH FACTOR RECEPTOR PEPTIDEE [auth I],
F [auth J],
G [auth K],
H [auth L]
5N/AMutation(s): 1 
UniProt & NIH Common Fund Data Resources
Find proteins for P08581 (Homo sapiens)
Explore P08581 
Go to UniProtKB:  P08581
PHAROS:  P08581
GTEx:  ENSG00000105976 
Entity Groups  
UniProt GroupP08581
Sequence Annotations
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  • Reference Sequence
Small Molecules
Modified Residues  1 Unique
IDChains TypeFormula2D DiagramParent
PTR
Query on PTR
E [auth I],
F [auth J],
G [auth K],
H [auth L]
L-PEPTIDE LINKINGC9 H12 N O6 PTYR
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 2.40 Å
  • R-Value Free: 0.270 
  • R-Value Work: 0.217 
  • R-Value Observed: 0.220 
  • Space Group: P 43 21 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 77.61α = 90
b = 77.61β = 90
c = 183.47γ = 90
Software Package:
Software NamePurpose
AMoREphasing
CNXrefinement
DENZOdata reduction
SCALEPACKdata scaling

Structure Validation

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Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2000-12-06
    Type: Initial release
  • Version 1.1: 2008-04-27
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2023-08-09
    Changes: Data collection, Database references, Derived calculations, Refinement description
  • Version 1.4: 2023-11-15
    Changes: Data collection