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2g35
From Proteopedia
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[[Image:2g35.gif|left|200px]] | [[Image:2g35.gif|left|200px]] | ||
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'''NMR structure of talin-PTB in complex with PIPKI''' | '''NMR structure of talin-PTB in complex with PIPKI''' | ||
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[[Category: Qin, J.]] | [[Category: Qin, J.]] | ||
[[Category: Wang, X.]] | [[Category: Wang, X.]] | ||
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| - | [[Category: | + | [[Category: Ptb domain]] |
| - | [[Category: | + | [[Category: Talin]] |
| - | + | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 04:38:14 2008'' | |
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Revision as of 01:38, 4 May 2008
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 Page seeded by OCA on Sun May 4 04:38:14 2008
Categories: Mus musculus | Single protein | Kong, X. | Misra, S. | Qin, J. | Wang, X. | Pipki | Ptb domain | Talin
