2fci

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Structural basis for the requirement of two phosphotyrosines in signaling mediated by Syk tyrosine kinase

Overview

The protein-tyrosine kinase Syk couples immune recognition receptors to, multiple signal transduction pathways, including the mobilization of, calcium and the activation of NFAT. The ability of Syk to regulate, signaling is influenced by its phosphorylation on tyrosine residues within, the linker B region. The phosphorylation of both Y342 and Y346 is, necessary for optimal signaling from the B cell receptor for antigen. The, SH2 domains of multiple signaling proteins share the ability to bind this, doubly phosphorylated site. The NMR structure of the C-terminal SH2 domain, of PLCgamma (PLCC) bound to a doubly phosphorylated Syk peptide reveals a, novel mode of phosphotyrosine recognition. PLCC undergoes extensive, conformational changes upon binding to form a second, phosphotyrosine-binding pocket in which pY346 is largely desolvated and, stabilized through electrostatic interactions. The formation of the second, binding pocket is distinct from other modes of phosphotyrosine recognition, in SH2-protein association. The dependence of signaling on simultaneous, phosphorylation of these two tyrosine residues offers a new mechanism to, fine-tune the cellular response to external stimulation.

About this Structure

2FCI is a Single protein structure of sequence from Bos taurus with ACE as ligand. Active as Transferase, with EC number and 2.7.10.2 2.7.10.1 and 2.7.10.2 Full crystallographic information is available from OCA.

Reference

Structural basis for the requirement of two phosphotyrosine residues in signaling mediated by Syk tyrosine kinase., Groesch TD, Zhou F, Mattila S, Geahlen RL, Post CB, J Mol Biol. 2006 Mar 10;356(5):1222-36. Epub 2005 Dec 27. PMID:16410013

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