1L2Z

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

Summary for 1L2Z

• Entry DOI: 10.2210/pdb1l2z/pdb
• Related: 1GYF
• Descriptor: CD2 ANTIGEN (CYTOPLASMIC TAIL)-BINDING PROTEIN 2, T-CELL SURFACE ANTIGEN CD2 (2 entities in total)
• Functional Keywords: gyf domain, protein-protein interaction, proline-rich peptide, cd2, cd2bp2, peptide binding-signaling protein complex, peptide binding/signaling protein
• Biological source: Homo sapiens (human); More
• Cellular location: Cytoplasm: O95400; Membrane; Single-pass type I membrane protein: P06729
• Total number of polymer chains: 2
• Total formula weight: 8560.43

Authors

Freund, C.,Kuhne, R.,Yang, H.,Park, S.,Reinherz, E.L.,Wagner, G. (deposition date: 2002-02-26, release date: 2002-11-20, Last modification date: 2024-05-22)

Primary citation

Freund, C.,Kuhne, R.,Yang, H.,Park, S.,Reinherz, E.L.,Wagner, G.
Dynamic interaction of CD2 with the GYF and the SH3 domain of compartmentalized effector molecules
Embo J., 21:5985-5995, 2002

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.

PubMed: 12426371
DOI: 10.1093/emboj/cdf602

Experimental method

SOLUTION NMR