1l2z
From Proteopedia
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==Overview== | ==Overview== | ||
| - | Intracellular protein interaction domains are essential for eukaryotic | + | 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. |
==About this Structure== | ==About this Structure== | ||
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[[Category: Kuhne, R.]] | [[Category: Kuhne, R.]] | ||
[[Category: Park, S.]] | [[Category: Park, S.]] | ||
| - | [[Category: Reinherz, E | + | [[Category: Reinherz, E L.]] |
[[Category: Wagner, G.]] | [[Category: Wagner, G.]] | ||
[[Category: Yang, H.]] | [[Category: Yang, H.]] | ||
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[[Category: protein-protein interaction]] | [[Category: protein-protein interaction]] | ||
| - | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Thu Feb 21 13:40:43 2008'' |
Revision as of 11:40, 21 February 2008
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CD2BP2-GYF domain in complex with proline-rich CD2 tail segment peptide
Overview
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.
About this Structure
1L2Z is a Protein complex structure of sequences from Homo sapiens. Full crystallographic information is available from OCA.
Reference
Dynamic interaction of CD2 with the GYF and the SH3 domain of compartmentalized effector molecules., Freund C, Kuhne R, Yang H, Park S, Reinherz EL, Wagner G, EMBO J. 2002 Nov 15;21(22):5985-95. PMID:12426371
Page seeded by OCA on Thu Feb 21 13:40:43 2008
