2G35
NMR structure of talin-PTB in complex with PIPKI
Summary for 2G35
| Entry DOI | 10.2210/pdb2g35/pdb |
| NMR Information | BMRB: 7061 |
| Descriptor | Talin-1, peptide (2 entities in total) |
| Functional Keywords | talin, ptb domain, pipki, structural protein |
| Biological source | Mus musculus (house mouse) |
| Cellular location | Cell projection, ruffle membrane; Peripheral membrane protein; Cytoplasmic side (By similarity): P26039 |
| Total number of polymer chains | 2 |
| Total formula weight | 12625.60 |
| Authors | |
| Primary citation | 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 Cited by 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: 16616931DOI: 10.1016/j.jmb.2006.02.048 PDB entries with the same primary citation |
| Experimental method | SOLUTION NMR |
Structure validation
Download full validation report
