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 language | English (US) |
|---|---|
| Article number | e01894-17 |
| Journal | mBio |
| Volume | 8 |
| Issue number | 6 |
| DOIs | |
| State | Published - Nov 1 2017 |
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Keywords
- Acetylphosphate
- Central metabolism
- Enolase
- Protein acetylation
- Proteomics
ASJC Scopus subject areas
- Microbiology
- Virology
Cite this
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 journal › Article
}
TY - JOUR
T1 - Ancient regulatory role of lysine acetylation in central metabolism
AU - Nakayasu, Ernesto S.
AU - Burnet, Meagan C.
AU - Walukiewicz, Hanna E.
AU - Wilkins, Christopher S.
AU - Shukla, Anil K.
AU - Brooks, Shelby
AU - Plutz, Matthew J.
AU - Lee, Brady D.
AU - Schilling, Birgit
AU - Wolfe, Alan J.
AU - Müller, Susanne
AU - Kirby, John R.
AU - Rao, Christopher V.
AU - Cort, John R.
AU - Payne, Samuel H.
PY - 2017/11/1
Y1 - 2017/11/1
N2 - 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.
AB - 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.
KW - Acetylphosphate
KW - Central metabolism
KW - Enolase
KW - Protein acetylation
KW - Proteomics
UR - http://www.scopus.com/inward/record.url?scp=85039922037&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85039922037&partnerID=8YFLogxK
U2 - 10.1128/mBio.01894-17
DO - 10.1128/mBio.01894-17
M3 - Article
C2 - 29184018
AN - SCOPUS:85039922037
VL - 8
JO - mBio
JF - mBio
SN - 2161-2129
IS - 6
M1 - e01894-17
ER -