A systematic screen for protein-lipid interactions in Saccharomyces cerevisiae

被引:129
|
作者
Gallego, Oriol [1 ]
Betts, Matthew J. [1 ]
Gvozdenovic-Jeremic, Jelena [1 ]
Maeda, Kenji [1 ]
Matetzki, Christian [1 ]
Aguilar-Gurrieri, Carmen [1 ]
Beltran-Alvarez, Pedro [1 ]
Bonn, Stefan [1 ]
Fernandez-Tornero, Carlos [1 ]
Jensen, Lars Juhl [1 ]
Kuhn, Michael [1 ]
Trott, Jamie [1 ]
Rybin, Vladimir [2 ]
Mueller, Christoph W. [1 ]
Bork, Peer [1 ]
Kaksonen, Marko [3 ]
Russell, Robert B. [1 ]
Gavin, Anne-Claude [1 ]
机构
[1] European Mol Biol Lab, Struct & Computat Biol Unit, D-69117 Heidelberg, Germany
[2] European Mol Biol Lab, Cell Biol & Biophys Unit, Heidelberg, Germany
[3] European Mol Biol Lab, Prot Express & Purificat Core Facil, Heidelberg, Germany
关键词
interactome; lipid-array; network; pleckstrin homology domains; sphingolipids; PLECKSTRIN-HOMOLOGY-DOMAIN; GLOBAL ANALYSIS; PH DOMAIN; BINDING; YEAST; PHOSPHOINOSITIDES; IDENTIFICATION; KINASES; GENOMES; SLM1;
D O I
10.1038/msb.2010.87
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Protein-metabolite networks are central to biological systems, but are incompletely understood. Here, we report a screen to catalog protein-lipid interactions in yeast. We used arrays of 56 metabolites to measure lipid-binding fingerprints of 172 proteins, including 91 with predicted lipid-binding domains. We identified 530 protein-lipid associations, the majority of which are novel. To show the data set's biological value, we studied further several novel interactions with sphingolipids, a class of conserved bioactive lipids with an elusive mode of action. Integration of live-cell imaging suggests new cellular targets for these molecules, including several with pleckstrin homology (PH) domains. Validated interactions with Slm1, a regulator of actin polarization, show that PH domains can have unexpected lipid-binding specificities and can act as coincidence sensors for both phosphatidylinositol phosphates and phosphorylated sphingolipids. Molecular Systems Biology 6: 430; published online 30 November 2010; doi:10.1038/msb.2010.87
引用
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页数:15
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