ArticleCommunications biology2021
Global mapping of protein-metabolite interactions in Saccharomyces cerevisiae reveals that Ser-Leu dipeptide regulates phosphoglycerate kinase activity.
Article in Communications biology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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21 citing papers in PubMed, 44 citations in OpenAlex.
- A single-amino-acid cleavage controls global mitochondrial complex integrity.Nature structural & molecular biology · 2026Article
- Discovery of regulatory complexes in Arabidopsis via protein-metabolite mapping during Pseudomonas infection.Plant physiology · 2026Article
- Article
- Multi-omics and palynology of selected Philippine forest honey.Scientific reports · 2026Article
- Mapping protein-metabolite interactions iniScience · 2025Article
- A century of studying plant secondary metabolism-From "what?" to "where, how, and why?"Plant physiology · 2024Review
- Challenges in the Metabolomics-Based Biomarker Validation Pipeline.Metabolites · 2024Review
- Decode protein-metabolite regulatory network: one MIDAS at a time.Signal transduction and targeted therapy · 2023Article
- MPI-VGAE: protein-metabolite enzymatic reaction link learning by variational graph autoencoders.Briefings in bioinformatics · 2023Article
- Network medicine: an approach to complex kidney disease phenotypes.Nature reviews. Nephrology · 2023Review
- The Knowns and Unknowns in Protein-Metabolite Interactions.International journal of molecular sciences · 2023Review
- Protein-Metabolite Interactions Shape Cellular Metabolism and Physiology.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Prediction of metabolite-protein interactions based on integration of machine learning and constraint-based modeling.Bioinformatics advances · 2023Article
- Rewiring of the protein-protein-metabolite interactome during the diauxic shift in yeast.Cellular and molecular life sciences : CMLS · 2022Article
- Past accomplishments and future challenges of the multi-omics characterization of leaf growth.Plant physiology · 2022Review
- 2',3'-cAMP treatment mimics the stress molecular response in Arabidopsis thaliana.Plant physiology · 2022Article
- An overview of technologies for MS-based proteomics-centric multi-omics.Expert review of proteomics · 2022Article
- Autophagy modulates the metabolism and growth of tomato fruit during development.Horticulture research · 2022Article
- Tyr-Asp inhibition of glyceraldehyde 3-phosphate dehydrogenase affects plant redox metabolism.The EMBO journal · 2021Article
- Proteogenic Dipeptides Are Characterized by Diel Fluctuations and Target of Rapamycin Complex-Signaling Dependency in the Model PlantFrontiers in plant science · 2021Article
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Authors and funding
21 authors at 7 institutions in 6 countries.
Funding
No grant is acknowledged in the PubMed record.
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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