2g35

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NMR structure of talin-PTB in complex with PIPKI

Overview

Phosphatidylinositol-4,5-bisphosphate (PIP2) is a key lipid messenger that, regulates myriad diverse cellular signaling pathways. To ensure, specificity in disparate cellular events, PIP2 must be localized to, specific sub-cellular sites. At PIP2-regulated focal adhesion (FA) sites, such localization is in part mediated via the recruitment and activation, of PIP2-producing enzyme, type Igamma phosphatidylinositol phosphate, kinase (PIPKIgamma), by a phosphotyrosine binding (PTB) domain of talin., Transient phosphorylation of PIPKIgamma at Y644 regulates the interaction, and efficient FA targeting of PIPKIgamma; however, the underlying, structural basis remains elusive. We have determined the NMR structure of, talin-1 PTB in complex with the Y644-phosphorylated PIPKIgamma fragment, (WVpYSPLH). As compared to canonical PTB domains that typically recognize, the NPXpY turn motif from a variety of signaling proteins, our structure, displays an unusual non-NPXpY-based recognition mode for talin-1 PTB where, K(357)RW in beta5 strand forms an antiparallel beta-sheet with the VpYS of, PIPKIgamma. A specific electrostatic triad between K357/R358 of talin-1, PTB and the pY644 of PIPKIgamma was observed, which is consistent with the, mutagenesis and isothermal calorimetry data. Combined with previous in, vivo data, our results provide a framework for understanding how, phosphorylation of Y644 in PIPKIgamma promotes its specific interaction, with talin-1, leading to efficient local synthesis of PIP2 and dynamic, regulation of integrin-mediated FA assembly.

About this Structure

2G35 is a Single protein structure of sequence from Mus musculus. Full crystallographic information is available from OCA.

Reference

Structural basis for the phosphorylation-regulated focal adhesion targeting of type Igamma phosphatidylinositol phosphate kinase (PIPKIgamma) by talin., Kong X, Wang X, Misra S, Qin J, J Mol Biol. 2006 May 26;359(1):47-54. Epub 2006 Mar 23. PMID:16616931

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