Extensive regulation of enzyme activity by phosphorylation in Escherichia coli

Evgeniya Schastnaya, Zrinka Raguz Nakic, Christoph H. Gruber, Peter Francis Doubleday, Aarti Krishnan, Nathan I. Johns, Jimin Park, Harris H. Wang and Uwe Sauer ()
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Evgeniya Schastnaya: Institute of Molecular Systems Biology, ETH Zurich
Zrinka Raguz Nakic: Institute of Molecular Systems Biology, ETH Zurich
Christoph H. Gruber: Institute of Molecular Systems Biology, ETH Zurich
Peter Francis Doubleday: Institute of Molecular Systems Biology, ETH Zurich
Aarti Krishnan: Institute of Molecular Systems Biology, ETH Zurich
Nathan I. Johns: Columbia University
Jimin Park: Columbia University
Harris H. Wang: Columbia University
Uwe Sauer: Institute of Molecular Systems Biology, ETH Zurich

Nature Communications, 2021, vol. 12, issue 1, 1-11

Abstract: Abstract Protein serine/threonine/tyrosine (S/T/Y) phosphorylation is an essential and frequent post-translational modification in eukaryotes, but historically has been considered less prevalent in bacteria because fewer proteins were found to be phosphorylated and most proteins were modified to a lower degree. Recent proteomics studies greatly expanded the phosphoproteome of Escherichia coli to more than 2000 phosphorylation sites (phosphosites), yet mechanisms of action were proposed for only six phosphosites and fitness effects were described for 38 phosphosites upon perturbation. By systematically characterizing functional relevance of S/T/Y phosphorylation in E. coli metabolism, we found 44 of the 52 mutated phosphosites to be functional based on growth phenotypes and intracellular metabolome profiles. By effectively doubling the number of known functional phosphosites, we provide evidence that protein phosphorylation is a major regulation process in bacterial metabolism. Combining in vitro and in vivo experiments, we demonstrate how single phosphosites modulate enzymatic activity and regulate metabolic fluxes in glycolysis, methylglyoxal bypass, acetate metabolism and the split between pentose phosphate and Entner-Doudoroff pathways through mechanisms that include shielding the substrate binding site, limiting structural dynamics, and disrupting interactions relevant for activity in vivo.

Date: 2021
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:12:y:2021:i:1:d:10.1038_s41467-021-25988-4

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DOI: 10.1038/s41467-021-25988-4

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