2g35

NMR structure of talin-PTB in complex with PIPKI

spinqualitylabelsall models 2g35, 20 NMR models Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image   Print3D Structural highlights 2g35 is a 2 chain structure with sequence from Lk3 transgenic mice. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance. NonStd Res: PTR Gene: Tln1, Tln (LK3 transgenic mice) Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum Function [TLN1_MOUSE] Probably involved in connections of major cytoskeletal structures to the plasma membrane. High molecular weight cytoskeletal protein concentrated at regions of cell-substratum contact and, in lymphocytes, at cell-cell contacts. Evolutionary Conservation Check, as determined by ConSurfDB. You may read the explanation of the method and the full data available from ConSurf. Publication Abstract from PubMed 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. 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 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Talin

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