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  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., 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.

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 Creators:
Luzarowski, M.1, Author              
Vicente, R.2, Author              
Kiselev, A.3, Author              
Wagner, M.3, Author              
Schlossarek, D.3, Author              
Erban, A.4, Author              
de Souza, L. P.5, Author              
Childs, Dorothee6, Author
Wojciechowska, I.1, Author              
Luzarowska, U.7, Author              
Gorka, M.3, Author              
Sokolowska, E.1, Author              
Kosmacz, M.1, Author              
Moreno, J.C.1, Author              
Brzezinska, A.3, Author              
Vegesna, B.3, Author              
Kopka, J.4, Author              
Fernie, A. R.5, Author              
Willmitzer, L.1, Author              
Ewald, Jennifer C.6, Author
Skirycz, A.3, Author               more..
Affiliations:
1Small Molecules, Department Willmitzer, Max Planck Institute of Molecular Plant Physiology, Max Planck Society, ou_1753340              
2System Regulation, Department Stitt, Max Planck Institute of Molecular Plant Physiology, Max Planck Society, ou_1753327              
3Small-Molecule Signalling, Department Willmitzer, Max Planck Institute of Molecular Plant Physiology, Max Planck Society, ou_2586692              
4Applied Metabolome Analysis, Department Willmitzer, Max Planck Institute of Molecular Plant Physiology, Max Planck Society, ou_1753338              
5Central Metabolism, Department Willmitzer, Max Planck Institute of Molecular Plant Physiology, Max Planck Society, ou_1753339              
6external, ou_persistent22              
7Genetics of Metabolic Traits, Cooperative Research Groups, Max Planck Institute of Molecular Plant Physiology, Max Planck Society, ou_2497694              

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 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.

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Language(s): eng - English
 Dates: 2021
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: -
 Identifiers: DOI: 10.1038/s42003-021-01684-3
Other: Luzarowski2021
 Degree: -

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Title: Communications Biology
Source Genre: Journal
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Publ. Info: London : Springer Nature
Pages: - Volume / Issue: 4 (1) Sequence Number: 181 Start / End Page: - Identifier: ISSN: 2399-3642
CoNE: https://pure.mpg.de/cone/journals/resource/2399-3642