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  3. Chemical Proteomic Profiling of Protein 4'-Phosphopantetheinylation in Mammalian Cells

Chemical Proteomic Profiling of Protein 4'-Phosphopantetheinylation in Mammalian Cells

  • Angew Chem Int Ed Engl. 2020 Sep 7;59(37):16069-16075. doi: 10.1002/anie.202004105.
Nan Chen 1,  Yuan Liu 1,  Yuanpei Li 1,  Chu Wang 1 2
Affiliations

Affiliations

  • 1 College of Chemistry and Molecular Engineering, Synthetic and Functional Biomolecules Center, Beijing National Laboratory for Molecular Sciences, Key Laboratory of Bioorganic Chemistry and Molecular Engineering of Ministry of Education, Peking University, Beijing, 100871, China.
  • 2 Peking-Tsinghua Center for Life Sciences, Peking University, China.
PMID: 32537878 DOI: 10.1002/anie.202004105
Abstract

Protein 4'-phosphopantetheinylation is an essential post-translational modification (PTM) in prokaryotes and eukaryotes. So far, only five protein substrates of this specific PTM have been discovered in mammalian cells. These proteins are known to perform important functions, including fatty acid biosynthesis and folate metabolism, as well as β-alanine activation. To explore existing and new substrates of 4'-phosphopantetheinylation in mammalian proteomes, we designed and synthesized a series of new pantetheine analogue probes, enabling effective metabolic labelling of 4'-phosphopantetheinylated proteins in HepG2 cells. In combination with a quantitative chemical proteomic platform, we enriched and identified all the currently known 4'-phosphopantetheinylated proteins with high confidence, and unambiguously determined their exact sites of modification. More encouragingly, we discovered, using targeted chemical proteomics, a potential 4'-phosphopantetheinylation site in the protein of mitochondrial dehydrogenase/reductase SDR family member 2 (DHRS2).

Keywords

chemical biology; mass spectrometry; metabolic labelling; phosphopantetheinylation; protein modifications.

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