1YWO

Phospholipase Cgamma1 SH3 in complex with a SLP-76 motif

Summary for 1YWO

• Entry DOI: 10.2210/pdb1ywo/pdb
• Descriptor: 1-phosphatidylinositol-4,5-bisphosphate phosphodiesterase gamma 1, Lymphocyte cytosolic protein 2 (3 entities in total)
• Functional Keywords: sh3, phospholipase c-gamma1, slp-76, sh2 domain-containing leukocyte phosphoprotein of 76 kd, hydrolase, signaling protein
• Biological source: Rattus norvegicus (Norway rat); More
• Cellular location: Cytoplasm (Probable): P10686; Cell projection, lamellipodium (By similarity): Q13094
• Total number of polymer chains: 2
• Total formula weight: 8561.63

Authors

Deng, L.,Velikovsky, C.A.,Swaminathan, C.P.,Cho, S.,Mariuzza, R.A. (deposition date: 2005-02-18, release date: 2005-08-16, Last modification date: 2024-02-14)

Primary citation

Deng, L.,Velikovsky, C.A.,Swaminathan, C.P.,Cho, S.,Mariuzza, R.A.
Structural Basis for Recognition of the T Cell Adaptor Protein SLP-76 by the SH3 Domain of Phospholipase Cgamma1
J.Mol.Biol., 352:1-10, 2005

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.

PubMed: 16061254
DOI: 10.1016/j.jmb.2005.06.072

Experimental method

X-RAY DIFFRACTION (1.81 Å)