1ywp: Difference between revisions
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'''Phospholipase Cgamma1 SH3''' | '''Phospholipase Cgamma1 SH3''' | ||
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[[Category: Swaminathan, C P.]] | [[Category: Swaminathan, C P.]] | ||
[[Category: Velikovsky, C A.]] | [[Category: Velikovsky, C A.]] | ||
[[Category: | [[Category: Phospholipase c-gamma1]] | ||
[[Category: | [[Category: Sh2 domain-containing leukocyte phosphoprotein of 76 kd]] | ||
[[Category: | [[Category: Sh3]] | ||
[[Category: | [[Category: Slp-76]] | ||
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Revision as of 16:53, 3 May 2008
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. 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 Page seeded by OCA on Sat May 3 16:53:27 2008