Abstract
ABSTRACTLysine 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.
Highlights
Lysine acetylation is a common protein post-translational modification in bacteria and eukaryotes
We found that lysine acetylation occurs in evolutionarily conserved lysine residues in catalytic sites of enzymes involved in central carbon metabolism
We investigated whether lysine acetylation is found on different enzymes and whether this modification is conserved throughout bacterial evolution by performing a comprehensive phyloproteomic analysis
Summary
Lysine acetylation is a common protein post-translational modification in bacteria and eukaryotes. We found that lysine acetylation occurs in evolutionarily conserved lysine residues in catalytic sites of enzymes involved in central carbon metabolism Previous work has shown that phosphoglycerate mutase (GpmA) and acetyl coenzyme A (acetyl-CoA) synthetase (Acs) both contain lysine residues within the catalytic active site, that acetylation of these residues abolishes enzyme function, and that subsequent deacetylation restores activity [4,5,6] These studies hint at a function for lysine acetylation, it is unclear whether this is an evolutionarily conserved and widespread mechanism. We found that acetylation occurs in conserved lysine residues located in catalytic pockets of enzymes from the glycolytic pathway and the TCA cycle Those modifications substantially changed the physical-chemical properties of the enzyme catalytic pocket inhibiting their activity
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
