A systematic screen for protein-lipid interactions in Saccharomyces cerevisiae

Mol Syst Biol. 2010 Nov 30:6:430. doi: 10.1038/msb.2010.87.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Algorithms
  • Fatty Acid-Binding Proteins / analysis
  • Fatty Acid-Binding Proteins / chemistry
  • Fatty Acid-Binding Proteins / metabolism
  • High-Throughput Screening Assays / methods*
  • Lipid Metabolism* / physiology
  • Lipid-Linked Proteins / analysis
  • Lipid-Linked Proteins / chemistry
  • Lipid-Linked Proteins / metabolism
  • Lipids / analysis
  • Metabolome
  • Models, Biological
  • Protein Array Analysis / methods
  • Protein Binding
  • Protein Interaction Domains and Motifs / physiology
  • Saccharomyces cerevisiae / chemistry*
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins / analysis*
  • Saccharomyces cerevisiae Proteins / chemistry
  • Saccharomyces cerevisiae Proteins / metabolism*
  • Validation Studies as Topic


  • Fatty Acid-Binding Proteins
  • Lipid-Linked Proteins
  • Lipids
  • Saccharomyces cerevisiae Proteins