Extensive In Vivo Metabolite-Protein Interactions Revealed by Large-Scale Systematic Analyses
Open accessAbstract
Natural small compounds comprise most cellular molecules and bind proteins as substrates, products, cofactors, and ligands. However, a large-scale investigation of in vivo protein-small metabolite interactions has not been performed. We developed a mass spectrometry assay for the large-scale identification of in vivo protein-hydrophobic small metabolite interactions in yeast and analyzed compounds that bind ergosterol biosynthetic proteins and protein kinases. Many of these proteins bind small metabolites; a few interactions were previously known, but the vast majority are new. Importantly, many key regulatory proteins such as protein kinases bind metabolites. Ergosterol was found to bind many proteins and may function as a general regulator. It is required for the activity of Ypk1, a mammalian AKT/SGK kinase homolog. Our study defines potential key regulatory steps in lipid biosynthetic pathways and suggests that small metabolites may play a more general role as regulators of protein activity and function than previously appreciated.
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Tandem affinity purification using tagged proteins and magnetic beads was demonstrated by Li et al. for the elucidation of small molecule-protein interactions in yeast.
“Use of this strategy was demonstrated by Li et al.79 for the elucidation of small molecule–protein interactions in yeast.”
From Connecting metabolome and phenotype: recent advances in functional metabolomics tools for the identification of bioactive natural products (2024) · cites this paper as [79]
The Results section describes tagged yeast proteins isolated with magnetic beads to identify associated small metabolites. Experimental Procedures describes one IgG-bead affinity capture followed by metabolite extraction, but does not describe a second purification step; the specific characterization as tandem affinity purification is therefore unsupported. (LLM, conf=0.85)
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- Authors
- Li, X., Gianoulis, T. A., Yip, K. Y., Gerstein, M., & Snyder, M.
- Affiliations
- Yale University (US)
- Corresponding author
- Snyder, Michael
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2010-11
- Volume
- 143
- Issue
- 4
- Pages
- 639-650
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC3005334
- OpenAlex
- W2010658450
- Cited by
- 237
- References
- 41
- Citations by year
- 2026: 7 · 2025: 11 · 2024: 10 · 2023: 16 · 2022: 14 · 2021: 14 · 2020: 6 · 2019: 13 · 2018: 14 · 2017: 15 · 2016: 13 · 2015: 24 · 2014: 13 · 2013: 26 · 2012: 16
- FWCI
- 8.59
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 989 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute of General Medical Sciences (R01GM062480)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fungal and yeast genetics research
- Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sphingolipid Metabolism and Signaling
- Keywords
- ergosterol, ergosterol biosynthesis, protein kinases, Ypk1, lipid biosynthesis regulation, yeast, mass spectrometry assay, protein regulation
- MeSH terms
- Ergosterol, Protein Kinases, Saccharomyces cerevisiae, Saccharomyces cerevisiae Proteins, Metabolome
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