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

Autor: Luzarowski M; Department of Molecular Physiology, Max Planck Institute of Molecular Plant Physiology, Potsdam, Germany. luzarowski@mpimp-golm.mpg.de., Vicente R; Department of Metabolic Networks, Max Planck Institute of Molecular Plant Physiology, Potsdam, Germany., Kiselev A; Department of Molecular Physiology, Max Planck Institute of Molecular Plant Physiology, Potsdam, Germany.; Laboratoire de Recherche en Sciences Végétales (LRSV), UPS/CNRS, UMR, Castanet Tolosan, France., Wagner M; Department of Molecular Physiology, Max Planck Institute of Molecular Plant Physiology, Potsdam, Germany.; University of Wrocław, Faculty of Biotechnology, Laboratory of Medical Biology, Wrocław, Poland., Schlossarek D; Department of Molecular Physiology, Max Planck Institute of Molecular Plant Physiology, Potsdam, Germany., Erban A; Department of Molecular Physiology, Max Planck Institute of Molecular Plant Physiology, Potsdam, Germany., de Souza LP; Department of Molecular Physiology, Max Planck Institute of Molecular Plant Physiology, Potsdam, Germany., Childs D; Department of Genome Biology, European Molecular Biology Laboratory, Heidelberg, Germany., Wojciechowska I; Department of Molecular Physiology, Max Planck Institute of Molecular Plant Physiology, Potsdam, Germany., Luzarowska U; Department of Molecular Physiology, Max Planck Institute of Molecular Plant Physiology, Potsdam, Germany.; Department of Life Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel., Górka M; Department of Molecular Physiology, Max Planck Institute of Molecular Plant Physiology, Potsdam, Germany., Sokołowska EM; Department of Molecular Physiology, Max Planck Institute of Molecular Plant Physiology, Potsdam, Germany., Kosmacz M; Department of Molecular Physiology, Max Planck Institute of Molecular Plant Physiology, Potsdam, Germany.; Center for Desert Agriculture, Biological and Environmental Science and Engineering Division (BESE), King Abdullah University of Science and Technology (KAUST), Thuwal, Saudi Arabia., Moreno JC; Department of Molecular Physiology, Max Planck Institute of Molecular Plant Physiology, Potsdam, Germany.; Center for Desert Agriculture, Biological and Environmental Science and Engineering Division (BESE), King Abdullah University of Science and Technology (KAUST), Thuwal, Saudi Arabia., Brzezińska A; Department of Molecular Physiology, Max Planck Institute of Molecular Plant Physiology, Potsdam, Germany., Vegesna B; Department of Molecular Physiology, Max Planck Institute of Molecular Plant Physiology, Potsdam, Germany., Kopka J; Department of Molecular Physiology, Max Planck Institute of Molecular Plant Physiology, Potsdam, Germany., Fernie AR; Department of Molecular Physiology, Max Planck Institute of Molecular Plant Physiology, Potsdam, Germany., Willmitzer L; Department of Molecular Physiology, Max Planck Institute of Molecular Plant Physiology, Potsdam, Germany., Ewald JC; Interfaculty Institute of Cell Biology, Eberhard Karls University of Tuebingen, Tuebingen, Germany., Skirycz A; Department of Molecular Physiology, Max Planck Institute of Molecular Plant Physiology, Potsdam, Germany. skirycz@mpimp-golm.mpg.de.; Boyce Thompson Institute, Ithaca, NY, USA. skirycz@mpimp-golm.mpg.de.
Jazyk: angličtina
Zdroj: Communications biology [Commun Biol] 2021 Feb 10; Vol. 4 (1), pp. 181. Date of Electronic Publication: 2021 Feb 10.
DOI: 10.1038/s42003-021-01684-3
Abstrakt: 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.
Databáze: MEDLINE
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