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A systematic screen for protein–lipid interactions in Saccharomyces cerevisiae

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Biological function emerges from the concerted action of numerous interacting biomolecules. Deciphering the molecular mechanisms behind cellular processes requires the systematic charting of the multitude of interactions between all cellular components. While protein–protein and protein– DNA networks have been the subject of many systematic surveys, others critically important cellular components, such as lipids, have to date rarely been studied in large-scale interaction screens. The importance of protein–lipid interactions is evident from the variety of protein domains that have evolved to bind particular lipids and from the large list of disorders, such as cancer and bipolar disorder, arising from altered protein–lipid interactions. The importance of lipids in biological processes and their under-representation in current biological networks suggest the need for systematic, unbiased biochemical screens. Here, we report a screen to catalog protein–lipid interactions in yeast using a lipid arrays. To illustrate 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. The dataset presented here represents an excellent resource to enhance the understanding of lipids function in eukaryotic systems

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