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| {{STRUCTURE_2g35| PDB=2g35 | SCENE= }} | | {{STRUCTURE_2g35| PDB=2g35 | SCENE= }} |
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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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| ==Overview==
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| 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.
| | The line below this paragraph, {{ABSTRACT_PUBMED_16616931}}, adds the Publication Abstract to the page |
| | (as it appears on PubMed at http://www.pubmed.gov), where 16616931 is the PubMed ID number. |
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| | {{ABSTRACT_PUBMED_16616931}} |
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| ==About this Structure== | | ==About this Structure== |
| 2G35 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full crystallographic information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2G35 OCA]. | | 2G35 is a [[Single protein]] structure of sequence from [http://en.wikipedia.org/wiki/Mus_musculus Mus musculus]. Full experimental information is available from [http://oca.weizmann.ac.il/oca-bin/ocashort?id=2G35 OCA]. |
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| ==Reference== | | ==Reference== |
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| [[Category: Ptb domain]] | | [[Category: Ptb domain]] |
| [[Category: Talin]] | | [[Category: Talin]] |
| ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun May 4 04:38:14 2008'' | | |
| | ''Page seeded by [http://oca.weizmann.ac.il/oca OCA ] on Sun Jul 27 19:56:38 2008'' |
