2FCI

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

Summary for 2FCI

• Entry DOI: 10.2210/pdb2fci/pdb
• Descriptor: Doubly phosphorylated peptide derived from Syk kinase comprising residues 338-350, C-termainl SH2 domain from phospholipase C-gamma-1 comprising residues 663-759 (2 entities in total)
• Functional Keywords: sh2 domain, phosphopeptide, syk kinase, plcgamma, plcc, hydrolase
• Biological source: Bos taurus (cattle); More
• Cellular location: Cell projection, lamellipodium (By similarity): P08487
• Total number of polymer chains: 2
• Total formula weight: 13975.43

Authors

Groesch, T.D.,Zhou, F.,Mattila, S.,Geahlen, R.L.,Post, C.B. (deposition date: 2005-12-12, release date: 2006-01-31, Last modification date: 2023-11-15)

Primary citation

Groesch, T.D.,Zhou, F.,Mattila, S.,Geahlen, R.L.,Post, C.B.
Structural basis for the requirement of two phosphotyrosine residues in signaling mediated by syk tyrosine kinase
J.Mol.Biol., 356:1222-1236, 2006

PubMed Abstract: 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.

PubMed: 16410013
DOI: 10.1016/j.jmb.2005.11.095

Experimental method

SOLUTION NMR