Ancient regulatory role of lysine acetylation in central metabolism

Ernesto S. Nakayasu, Meagan C. Burnet, Hanna E. Walukiewicz, Christopher S. Wilkins, Anil K. Shukla, Shelby Brooks, Matthew J. Plutz, Brady D. Lee, Birgit Schilling, Alan J. Wolfe, Susanne Müller, John R. Kirby, Christopher V. Rao, John R. Cort, Samuel H. Payne

Research output: Contribution to journalArticle

Abstract

Lysine acetylation is a common protein post-translational modification in bacteria and eukaryotes. Unlike phosphorylation, whose functional role in signaling has been established, it is unclear what regulatory mechanism acetylation plays and whether it is conserved across evolution. By performing a proteomic analysis of 48 phylogenetically distant bacteria, we discovered conserved acetylation sites on catalytically essential lysine residues that are invariant throughout evolution. Lysine acetylation removes the residue’s charge and changes the shape of the pocket required for substrate or cofactor binding. Two-thirds of glycolytic and tricarboxylic acid (TCA) cycle enzymes are acetylated at these critical sites. Our data suggest that acetylation may play a direct role in metabolic regulation by switching off enzyme activity. We propose that protein acetylation is an ancient and widespread mechanism of protein activity regulation. IMPORTANCE Post-translational modifications can regulate the activity and localization of proteins inside the cell. Similar to phosphorylation, lysine acetylation is present in both eukaryotes and prokaryotes and modifies hundreds to thousands of proteins in cells. However, how lysine acetylation regulates protein function and whether such a mechanism is evolutionarily conserved is still poorly understood. Here, we investigated evolutionary and functional aspects of lysine acetylation by searching for acetylated lysines in a comprehensive proteomic data set from 48 phylogenetically distant bacteria. We found that lysine acetylation occurs in evolutionarily conserved lysine residues in catalytic sites of enzymes involved in central carbon metabolism. Moreover, this modification inhibits enzymatic activity. Our observations suggest that lysine acetylation is an evolutionarily conserved mechanism of controlling central metabolic activity by directly blocking enzyme active sites.

Original languageEnglish (US)
Article numbere01894-17
JournalmBio
Volume8
Issue number6
DOIs
StatePublished - Nov 1 2017

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Acetylation
Lysine
Enzymes
Post Translational Protein Processing
Proteins
Eukaryota
Bacteria
Proteomics
Catalytic Domain
Phosphorylation
Citric Acid Cycle
Carbon

Keywords

  • Acetylphosphate
  • Central metabolism
  • Enolase
  • Protein acetylation
  • Proteomics

ASJC Scopus subject areas

  • Microbiology
  • Virology

Cite this

Nakayasu, E. S., Burnet, M. C., Walukiewicz, H. E., Wilkins, C. S., Shukla, A. K., Brooks, S., ... Payne, S. H. (2017). Ancient regulatory role of lysine acetylation in central metabolism. mBio, 8(6), [e01894-17]. https://doi.org/10.1128/mBio.01894-17

Ancient regulatory role of lysine acetylation in central metabolism. / Nakayasu, Ernesto S.; Burnet, Meagan C.; Walukiewicz, Hanna E.; Wilkins, Christopher S.; Shukla, Anil K.; Brooks, Shelby; Plutz, Matthew J.; Lee, Brady D.; Schilling, Birgit; Wolfe, Alan J.; Müller, Susanne; Kirby, John R.; Rao, Christopher V.; Cort, John R.; Payne, Samuel H.

In: mBio, Vol. 8, No. 6, e01894-17, 01.11.2017.

Research output: Contribution to journalArticle

Nakayasu, ES, Burnet, MC, Walukiewicz, HE, Wilkins, CS, Shukla, AK, Brooks, S, Plutz, MJ, Lee, BD, Schilling, B, Wolfe, AJ, Müller, S, Kirby, JR, Rao, CV, Cort, JR & Payne, SH 2017, 'Ancient regulatory role of lysine acetylation in central metabolism', mBio, vol. 8, no. 6, e01894-17. https://doi.org/10.1128/mBio.01894-17
Nakayasu ES, Burnet MC, Walukiewicz HE, Wilkins CS, Shukla AK, Brooks S et al. Ancient regulatory role of lysine acetylation in central metabolism. mBio. 2017 Nov 1;8(6). e01894-17. https://doi.org/10.1128/mBio.01894-17
Nakayasu, Ernesto S. ; Burnet, Meagan C. ; Walukiewicz, Hanna E. ; Wilkins, Christopher S. ; Shukla, Anil K. ; Brooks, Shelby ; Plutz, Matthew J. ; Lee, Brady D. ; Schilling, Birgit ; Wolfe, Alan J. ; Müller, Susanne ; Kirby, John R. ; Rao, Christopher V. ; Cort, John R. ; Payne, Samuel H. / Ancient regulatory role of lysine acetylation in central metabolism. In: mBio. 2017 ; Vol. 8, No. 6.
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