Crystal structure of the C-terminal SH3 domain of the adaptor protein GADS in complex with SLP-76 motif peptide reveals a unique SH3-SH3 interaction.
The Grb2-like adaptor protein GADS is essential for tyrosine kinase-dependent signaling in T lymphocytes. Following T cell receptor ligation, GADS interacts through its C-terminal SH3 domain with the adaptors SLP-76 and LAT, to form a multiprotein signaling complex that is crucial for T cell activation. To understand the structural basis for the selective recognition of GADS by SLP-76, herein is reported the crystal structure at 1.54 Angstrom of the C-terminal SH3 domain of GADS bound to the SLP-76 motif 233-PSIDRSTKP-241, which represents the minimal binding site. In addition to the unique structural features adopted by the bound SLP-76 peptide, the complex structure reveals a unique SH3-SH3 interaction. This homophilic interaction, which is observed in presence of the SLP-76 peptide and is present in solution, extends our understanding of the molecular mechanisms that could be employed by modular proteins to increase their signaling transduction specificity.
Dimasi
Nazzareno
N
Laboratory for Molecular Medicine, Istituto Giannina Gaslini, Largo Gerolamo Gaslini 5, Genova 16147, Italy. ndimasi@gmail.com
D048868:Adaptor Proteins, Signal Transducing / Q000737:chemistry* / Q000378:metabolism; D020816:Amino Acid Motifs; D018360:Crystallography, X-Ray; D006801:Humans; D008213:Lymphocyte Activation / Q000502:physiology; D046912:Multiprotein Complexes / Q000737:chemistry* / Q000378:metabolism; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism; D010750:Phosphoproteins / Q000737:chemistry* / Q000378:metabolism; D020836:Protein Structure, Quaternary; D017434:Protein Structure, Tertiary; D015398:Signal Transduction / Q000502:physiology; D013601:T-Lymphocytes / Q000737:chemistry / Q000378:metabolism
D048868:Adaptor Proteins, Signal Transducing; C409587:GRAP2 protein, human; D046912:Multiprotein Complexes; D010455:Peptides; D010750:Phosphoproteins; C092947:SLP-76 signal Transducing adaptor proteins