A systematic screen for protein-lipid interactions in Saccharomyces cerevisiae.
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.
Structural and Computational Biology Unit, European Molecular Biology Laboratory, EMBL, Heidelberg, Germany.
Oriol
O
Gallego
Matthew J
MJ
Betts
Jelena
J
Gvozdenovic-Jeremic
Kenji
K
Maeda
Christian
C
Matetzki
Carmen
C
Aguilar-Gurrieri
Pedro
P
Beltran-Alvarez
Stefan
S
Bonn
Carlos
C
Fernández-Tornero
Lars Juhl
LJ
Jensen
Michael
M
Kuhn
Jamie
J
Trott
Vladimir
V
Rybin
Christoph W
CW
Müller
Peer
P
Bork
Marko
M
Kaksonen
Robert B
RB
Russell
Anne-Claude
AC
Gavin
D000465:Algorithms; D050556:Fatty Acid-Binding Proteins / Q000032:analysis / Q000737:chemistry / Q000378:metabolism; D057166:High-Throughput Screening Assays / Q000379:methods*; D050356:Lipid Metabolism / Q000502:physiology; D058635:Lipid-Linked Proteins / Q000032:analysis / Q000737:chemistry / Q000378:metabolism; D008055:Lipids / Q000032:analysis; D055442:Metabolome; D008954:Models, Biological; D040081:Protein Array Analysis / Q000379:methods; D011485:Protein Binding; D054730:Protein Interaction Domains and Motifs / Q000502:physiology; D012441:Saccharomyces cerevisiae / Q000737:chemistry* / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins / Q000032:analysis* / Q000737:chemistry / Q000378:metabolism*; D054928:Validation Studies as Topic
D050556:Fatty Acid-Binding Proteins; D058635:Lipid-Linked Proteins; D008055:Lipids; D029701:Saccharomyces cerevisiae Proteins