2G35

NMR structure of talin-PTB in complex with PIPKI

2G35 の概要

• エントリーDOI: 10.2210/pdb2g35/pdb
• NMR情報: BMRB: 7061
• 分子名称: Talin-1, peptide (2 entities in total)
• 機能のキーワード: talin, ptb domain, pipki, structural protein
• 由来する生物種: Mus musculus (house mouse)
• 細胞内の位置: Cell projection, ruffle membrane; Peripheral membrane protein; Cytoplasmic side (By similarity): P26039
• タンパク質・核酸の鎖数: 2
• 化学式量合計: 12625.60

構造登録者

Kong, X.,Wang, X.,Misra, S.,Qin, J. (登録日: 2006-02-17, 公開日: 2006-05-02, 最終更新日: 2024-10-30)

主引用文献

Kong, X.,Wang, X.,Misra, S.,Qin, J.
Structural Basis for the Phosphorylation-regulated Focal Adhesion Targeting of Type Igamma Phosphatidylinositol Phosphate Kinase (PIPKIgamma) by Talin.
J.Mol.Biol., 359:47-54, 2006

PubMed Abstract: 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.

PubMed: 16616931
DOI: 10.1016/j.jmb.2006.02.048

実験手法

SOLUTION NMR