Global mapping of protein–metabolite interactions in Saccharomyces cerevisiae reveals that Ser-Leu dipeptide regulates phosphoglycerate kinase activity

Marcin Luzarowski, Rubén Vicente, Andrei Kiselev, Mateusz Wagner, Dennis Schlossarek, Alexander Erban, Leonardo Perez de Souza, Dorothee Childs, Izabela Wojciechowska, Urszula Luzarowska, Michał Górka, Ewelina M. Sokołowska, Monika Kosmacz, Juan C. Moreno, Aleksandra Brzezińska, Bhavana Vegesna, Joachim Kopka, Alisdair R. Fernie, Lothar Willmitzer, Jennifer C. EwaldAleksandra Skirycz

Research output: Contribution to journalArticlepeer-review

Abstract

AbstractProtein–metabolite interactions are of crucial importance for all cellular processes but remain understudied. Here, we applied a biochemical approach named PROMIS, to address the complexity of the protein–small molecule interactome in the model yeast Saccharomyces cerevisiae. By doing so, we provide a unique dataset, which can be queried for interactions between 74 small molecules and 3982 proteins using a user-friendly interface available at https://promis.mpimp-golm.mpg.de/yeastpmi/. By interpolating PROMIS with the list of predicted protein–metabolite interactions, we provided experimental validation for 225 binding events. Remarkably, of the 74 small molecules co-eluting with proteins, 36 were proteogenic dipeptides. Targeted analysis of a representative dipeptide, Ser-Leu, revealed numerous protein interactors comprising chaperones, proteasomal subunits, and metabolic enzymes. We could further demonstrate that Ser-Leu binding increases activity of a glycolytic enzyme phosphoglycerate kinase (Pgk1). Consistent with the binding analysis, Ser-Leu supplementation leads to the acute metabolic changes and delays timing of a diauxic shift. Supported by the dipeptide accumulation analysis our work attests to the role of Ser-Leu as a metabolic regulator at the interface of protein degradation and central metabolism.
Original languageEnglish (US)
JournalCommunications Biology
Volume4
Issue number1
DOIs
StatePublished - Feb 10 2021

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