1ywp
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Phospholipase Cgamma1 SH3
OverviewOverview
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.
About this StructureAbout this Structure
1YWP is a Single protein structure of sequence from Rattus norvegicus. Active as Phosphoinositide phospholipase C, with EC number 3.1.4.11 Full crystallographic information is available from OCA.
ReferenceReference
Structural basis for recognition of the T cell adaptor protein SLP-76 by the SH3 domain of phospholipase Cgamma1., Deng L, Velikovsky CA, Swaminathan CP, Cho S, Mariuzza RA, J Mol Biol. 2005 Sep 9;352(1):1-10. PMID:16061254
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