1L2Z

CD2BP2-GYF domain in complex with proline-rich CD2 tail segment peptide


Experimental Data Snapshot

  • Method: SOLUTION NMR
  • Conformers Calculated: 100 
  • Conformers Submitted: 15 
  • Selection Criteria: structures with the lowest energy 

wwPDB Validation   3D Report Full Report


This is version 1.3 of the entry. See complete history


Literature

Dynamic interaction of CD2 with the GYF and the SH3 domain of compartmentalized effector molecules

Freund, C.Kuhne, R.Yang, H.Park, S.Reinherz, E.L.Wagner, G.

(2002) EMBO J 21: 5985-5995

  • DOI: https://doi.org/10.1093/emboj/cdf602
  • Primary Citation of Related Structures:  
    1L2Z

  • PubMed Abstract: 

    Intracellular protein interaction domains are essential for eukaryotic signaling. In T cells, the CD2BP2 adaptor binds two membrane-proximal proline-rich motifs in the CD2 cytoplasmic tail via its GYF domain, thereby regulating interleukin-2 production. Here we present the structure of the GYF domain in complex with a CD2 tail peptide. Unlike SH3 domains, which use two surface pockets to accommodate proline residues of ligands, the GYF domain employs phylogenetically conserved hydrophobic residues to create a single interaction surface. NMR analysis shows that the Fyn but not the Lck tyrosine kinase SH3 domain competes with CD2BP2 GYF-domain binding to the same CD2 proline-rich sequence in vitro. To test the in vivo significance of this competition, we used co-immunoprecipitation experiments and found that CD2BP2 is the ligand of the membrane-proximal proline-rich tandem repeat of CD2 in detergent-soluble membrane compartments, but is replaced by Fyn SH3 after CD2 is translocated into lipid rafts upon CD2 ectodomain clustering. This unveils the mechanism of a switch of CD2 function due to an extracellular mitogenic signal.


  • Organizational Affiliation

    Protein Engineering Group and Molecular Modeling Group, Forschungsinstitut für Molekulare Pharmakologie and Freie Universität Berlin, Robert-Rössle-Strasse 10, D-13125 Berlin, Germany. freund@fmp-berlin.de


Macromolecules
Find similar proteins by:  (by identity cutoff)  |  3D Structure
Entity ID: 1
MoleculeChains Sequence LengthOrganismDetailsImage
CD2 ANTIGEN (CYTOPLASMIC TAIL)-BINDING PROTEIN 262Homo sapiensMutation(s): 0 
Gene Names: CD2BP2 (amino acids 280-341)
UniProt & NIH Common Fund Data Resources
Find proteins for O95400 (Homo sapiens)
Explore O95400 
Go to UniProtKB:  O95400
PHAROS:  O95400
GTEx:  ENSG00000169217 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupO95400
Sequence Annotations
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  • Reference Sequence

Find similar proteins by:  Sequence   |   3D Structure  

Entity ID: 2
MoleculeChains Sequence LengthOrganismDetailsImage
T-CELL SURFACE ANTIGEN CD211N/AMutation(s): 0 
UniProt & NIH Common Fund Data Resources
Find proteins for P06729 (Homo sapiens)
Explore P06729 
Go to UniProtKB:  P06729
PHAROS:  P06729
GTEx:  ENSG00000116824 
Entity Groups  
Sequence Clusters30% Identity50% Identity70% Identity90% Identity95% Identity100% Identity
UniProt GroupP06729
Sequence Annotations
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  • Reference Sequence
Experimental Data & Validation

Experimental Data

  • Method: SOLUTION NMR
  • Conformers Calculated: 100 
  • Conformers Submitted: 15 
  • Selection Criteria: structures with the lowest energy 

Structure Validation

View Full Validation Report



Entry History 

Deposition Data

Revision History  (Full details and data files)

  • Version 1.0: 2002-11-20
    Type: Initial release
  • Version 1.1: 2008-04-28
    Changes: Version format compliance
  • Version 1.2: 2011-07-13
    Changes: Version format compliance
  • Version 1.3: 2022-02-23
    Changes: Database references, Derived calculations