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

Luzarowski, M.; Vicente, R.; Kiselev, A.; Wagner, M.; Schlossarek, D.; Erban, A.; de Souza, L. P.; Childs, Dorothee; Wojciechowska, I.; Luzarowska, U.; Gorka, M.; Sokolowska, E.; Kosmacz, M.; Moreno, J.C.; Brzezinska, A.; Vegesna, B.; Kopka, J.; Fernie, A. R.; Willmitzer, L.; Ewald, Jennifer C.; Skirycz, A.

doi:10.1038/s42003-021-01684-3

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

MPS-Authors

/persons/resource/persons202693

Luzarowski, M.
Small Molecules, Department Willmitzer, Max Planck Institute of Molecular Plant Physiology, Max Planck Society;

/persons/resource/persons229319

Vicente, R.
System Regulation, Department Stitt, Max Planck Institute of Molecular Plant Physiology, Max Planck Society;

/persons/resource/persons257061

Kiselev, A.
Small-Molecule Signalling, Department Willmitzer, Max Planck Institute of Molecular Plant Physiology, Max Planck Society;

/persons/resource/persons247515

Wagner, M.
Small-Molecule Signalling, Department Willmitzer, Max Planck Institute of Molecular Plant Physiology, Max Planck Society;

/persons/resource/persons243167

Schlossarek, D.
Small-Molecule Signalling, Department Willmitzer, Max Planck Institute of Molecular Plant Physiology, Max Planck Society;

/persons/resource/persons97140

Erban, A.
Applied Metabolome Analysis, Department Willmitzer, Max Planck Institute of Molecular Plant Physiology, Max Planck Society;

/persons/resource/persons134057

de Souza, L. P.
Central Metabolism, Department Willmitzer, Max Planck Institute of Molecular Plant Physiology, Max Planck Society;

/persons/resource/persons225469

Wojciechowska, I.
Small Molecules, Department Willmitzer, Max Planck Institute of Molecular Plant Physiology, Max Planck Society;

/persons/resource/persons250183

Luzarowska, U.
Genetics of Metabolic Traits, Cooperative Research Groups, Max Planck Institute of Molecular Plant Physiology, Max Planck Society;

/persons/resource/persons183352

Gorka, M.
Small-Molecule Signalling, Department Willmitzer, Max Planck Institute of Molecular Plant Physiology, Max Planck Society;

/persons/resource/persons97419

Sokolowska, E.
Small Molecules, Department Willmitzer, Max Planck Institute of Molecular Plant Physiology, Max Planck Society;

/persons/resource/persons97243

Kosmacz, M.
Small Molecules, Department Willmitzer, Max Planck Institute of Molecular Plant Physiology, Max Planck Society;

/persons/resource/persons192949

Moreno, J.C.
Small Molecules, Department Willmitzer, Max Planck Institute of Molecular Plant Physiology, Max Planck Society;

/persons/resource/persons257020

Brzezinska, A.
Small-Molecule Signalling, Department Willmitzer, Max Planck Institute of Molecular Plant Physiology, Max Planck Society;

/persons/resource/persons257063

Vegesna, B.
Small-Molecule Signalling, Department Willmitzer, Max Planck Institute of Molecular Plant Physiology, Max Planck Society;

/persons/resource/persons97239

Kopka, J.
Applied Metabolome Analysis, Department Willmitzer, Max Planck Institute of Molecular Plant Physiology, Max Planck Society;

/persons/resource/persons97147

Fernie, A. R.
Central Metabolism, Department Willmitzer, Max Planck Institute of Molecular Plant Physiology, Max Planck Society;

/persons/resource/persons97481

Willmitzer, L.
Small Molecules, Department Willmitzer, Max Planck Institute of Molecular Plant Physiology, Max Planck Society;

/persons/resource/persons199927

Skirycz, A.
Small-Molecule Signalling, Department Willmitzer, Max Planck Institute of Molecular Plant Physiology, Max Planck Society;

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Citation

Luzarowski, M., Vicente, R., Kiselev, A., Wagner, M., Schlossarek, D., Erban, A., et al. (2021). Global mapping of protein–metabolite interactions in Saccharomyces cerevisiae reveals that Ser-Leu dipeptide regulates phosphoglycerate kinase activity. Communications Biology, 4(1): 181. doi:10.1038/s42003-021-01684-3.

Cite as: https://hdl.handle.net/21.11116/0000-0007-F787-A

Abstract

Protein–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.