2g35: Difference between revisions

Revision as of 04:38, 4 May 2008

NMR structure of talin-PTB in complex with PIPKI

OverviewOverview

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 StructureAbout this Structure

2G35 is a Single protein structure of sequence from Mus musculus. Full crystallographic information is available from OCA.

ReferenceReference

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

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OCA

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 [[Image:2g35.gif|left|200px]]
- {{Structure
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-|GENE= Tln1, Tln ([http://www.ncbi.nlm.nih.gov/Taxonomy/Browser/wwwtax.cgi?mode=Info&srchmode=5&id=10090 Mus musculus])
+-->
-|DOMAIN=
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-|RELATEDENTRY=
-|RESOURCES=<span class='plainlinks'>[http://oca.weizmann.ac.il/oca-docs/fgij/fg.htm?mol=2g35 FirstGlance], [http://oca.weizmann.ac.il/oca-bin/ocaids?id=2g35 OCA], [http://www.ebi.ac.uk/pdbsum/2g35 PDBsum], [http://www.rcsb.org/pdb/explore.do?structureId=2g35 RCSB]</span>
-}}
 '''NMR structure of talin-PTB in complex with PIPKI'''
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 [[Category: Qin, J.]]
 [[Category: Wang, X.]]
-[[Category: pipki]]
+[[Category: Pipki]]
-[[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 Mon Mar 31 03:11:10 2008''