1YWO

Phospholipase Cgamma1 SH3 in complex with a SLP-76 motif


Experimental Data Snapshot

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.81 Å
  • R-Value Free: 0.221 
  • R-Value Work: 0.171 
  • R-Value Observed: 0.173 

wwPDB Validation   3D Report Full Report


This is version 1.4 of the entry. See complete history


Literature

Structural Basis for Recognition of the T Cell Adaptor Protein SLP-76 by the SH3 Domain of Phospholipase Cgamma1

Deng, L.Velikovsky, C.A.Swaminathan, C.P.Cho, S.Mariuzza, R.A.

(2005) J Mol Biol 352: 1-10

  • DOI: https://doi.org/10.1016/j.jmb.2005.06.072
  • Primary Citation of Related Structures:  
    1YWO, 1YWP

  • PubMed Abstract: 

    The enzyme phospholipase Cgamma1 (PLCgamma1) is essential for T cell signaling and activation. Following T cell receptor ligation, PLCgamma1 interacts through its SH2 and SH3 domains with the adaptors LAT and SLP-76, respectively, to form a multiprotein signaling complex that leads to activation of PLCgamma1 by Syk tyrosine kinases. To identify the binding site for PLCgamma1 in SLP-76, we used isothermal titration calorimetry to measure affinities for the interaction of PLCgamma1-SH3 with a set of overlapping peptides spanning the central proline-rich region of SLP-76. PLCgamma1-SH3 bound with high specificity to the SLP-76 motif 186PPVPPQRP193, which represents the minimal binding site. To understand the basis for selective recognition, we determined the crystal structures of PLCgamma1-SH3 in free form, and bound to a 10-mer peptide containing this site, to resolutions of 1.60 A and 1.81 A, respectively. The structures reveal that several key contacting residues of the SH3 shift toward the SLP-76 peptide upon complex formation, optimizing the fit and strengthening hydrophobic interactions. Selectivity results mainly from strict shape complementarity between protein and peptide, rather than sequence-specific hydrogen bonding. In addition, Pro193 of SLP-76 assists in positioning Arg192 into the compass pocket of PLCgamma1-SH3, which coordinates the compass residue through an unusual aspartate. The PLCgamma1-SH3/SLP-76 structure provides insights into ligand binding by SH3 domains related to PLCgamma1-SH3, as well as into recognition by PLCgamma1 of signaling partners other than SLP-76.


  • Organizational Affiliation

    Center for Advanced Research in Biotechnology, W. M. Keck Laboratory for Structural Biology, University of Maryland Biotechnology Institute, Rockville, MD 20850, USA.


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
1-phosphatidylinositol-4,5-bisphosphate phosphodiesterase gamma 164Rattus norvegicusMutation(s): 1 
Gene Names: Plcg1
EC: 3.1.4.11
UniProt
Find proteins for P10686 (Rattus norvegicus)
Explore P10686 
Go to UniProtKB:  P10686
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP10686
Sequence Annotations
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  • Reference Sequence

Find similar proteins by:  Sequence   |   3D Structure  

Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
Lymphocyte cytosolic protein 2B [auth P]10Homo sapiensMutation(s): 0 
UniProt & NIH Common Fund Data Resources
Find proteins for Q13094 (Homo sapiens)
Explore Q13094 
Go to UniProtKB:  Q13094
PHAROS:  Q13094
GTEx:  ENSG00000043462 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupQ13094
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: X-RAY DIFFRACTION
  • Resolution: 1.81 Å
  • R-Value Free: 0.221 
  • R-Value Work: 0.171 
  • R-Value Observed: 0.173 
  • Space Group: P 43 21 2
Unit Cell:
Length ( Å )Angle ( ˚ )
a = 46.723α = 90
b = 46.723β = 90
c = 58.112γ = 90
Software Package:
Software NamePurpose
REFMACrefinement
HKL-2000data reduction
SCALEPACKdata scaling
PHASESphasing

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2005-08-16
    Type: Initial release
  • Version 1.1: 2008-04-30
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Advisory, Version format compliance
  • Version 1.3: 2021-10-20
    Changes: Database references
  • Version 1.4: 2024-02-14
    Changes: Data collection