Ancient Regulatory Role of Lysine Acetylation in Central Metabolism
Abstract
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 inmore »
- Authors:
-
- Biological Sciences Division, Pacific Northwest National Laboratory, Richland, Washington, USA
- Department of Chemical and Biomolecular Engineering, University of Illinois at Urbana-Champaign, Urbana, Illinois, USA
- Earth Systems Science Division, Pacific Northwest National Laboratory, Richland, Washington, USA
- Buck Institute for Research on Aging, Novato, California, USA
- Department of Microbiology and Immunology, Stritch School of Medicine, Health Sciences Division, Loyola University Chicago, Maywood, Illinois, USA
- Department of Microbiology and Immunology, Medical College of Wisconsin, Milwaukee, Wisconsin, USA
- Publication Date:
- Sponsoring Org.:
- USDOE
- OSTI Identifier:
- 1437780
- Grant/Contract Number:
- SC0012443; Early Career Award Program; Pan-omics Program
- Resource Type:
- Published Article
- Journal Name:
- mBio
- Additional Journal Information:
- Journal Name: mBio Journal Volume: 8 Journal Issue: 6; Journal ID: ISSN 2161-2129
- Publisher:
- American Society for Microbiology
- Country of Publication:
- United States
- Language:
- English
Citation Formats
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., Msadek, ed., Tarek, Laub, Michael, and Finkel, Steven. Ancient Regulatory Role of Lysine Acetylation in Central Metabolism. United States: N. p., 2017.
Web. doi: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., Msadek, ed., Tarek, Laub, Michael, & Finkel, Steven. Ancient Regulatory Role of Lysine Acetylation in Central Metabolism. United States. 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., Msadek, ed., Tarek, Laub, Michael, and Finkel, Steven. Fri .
"Ancient Regulatory Role of Lysine Acetylation in Central Metabolism". United States. https://doi.org/10.1128/mBio.01894-17.
@article{osti_1437780,
title = {Ancient Regulatory Role of Lysine Acetylation in Central Metabolism},
author = {Nakayasu, Ernesto S. and Burnet, Meagan C. and Walukiewicz, Hanna E. and Wilkins, Christopher S. and Shukla, Anil K. and Brooks, Shelby and Plutz, Matthew J. and Lee, Brady D. and Schilling, Birgit and Wolfe, Alan J. and Müller, Susanne and Kirby, John R. and Rao, Christopher V. and Cort, John R. and Payne, Samuel H. and Msadek, ed., Tarek and Laub, Michael and Finkel, Steven},
abstractNote = {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.},
doi = {10.1128/mBio.01894-17},
journal = {mBio},
number = 6,
volume = 8,
place = {United States},
year = {Fri Dec 29 00:00:00 EST 2017},
month = {Fri Dec 29 00:00:00 EST 2017}
}
https://doi.org/10.1128/mBio.01894-17
Web of Science
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