Ancient Regulatory Role of Lysine Acetylation in Central Metabolism

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 perf...

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Autores principales:	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
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2017
Materias:	acetylphosphate central metabolism enolase protein acetylation proteomics Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/3609a2a8164d44b5be96efbb71d34c8d
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spelling	oai:doaj.org-article:3609a2a8164d44b5be96efbb71d34c8d2021-11-15T15:51:55ZAncient Regulatory Role of Lysine Acetylation in Central Metabolism10.1128/mBio.01894-172150-7511https://doaj.org/article/3609a2a8164d44b5be96efbb71d34c8d2017-12-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mBio.01894-17https://doaj.org/toc/2150-7511ABSTRACT 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.Ernesto S. NakayasuMeagan C. BurnetHanna E. WalukiewiczChristopher S. WilkinsAnil K. ShuklaShelby BrooksMatthew J. PlutzBrady D. LeeBirgit SchillingAlan J. WolfeSusanne MüllerJohn R. KirbyChristopher V. RaoJohn R. CortSamuel H. PayneAmerican Society for Microbiologyarticleacetylphosphatecentral metabolismenolaseprotein acetylationproteomicsMicrobiologyQR1-502ENmBio, Vol 8, Iss 6 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	acetylphosphate central metabolism enolase protein acetylation proteomics Microbiology QR1-502
spellingShingle	acetylphosphate central metabolism enolase protein acetylation proteomics Microbiology QR1-502 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 Ancient Regulatory Role of Lysine Acetylation in Central Metabolism
description	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.
format	article
author	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
author_facet	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
author_sort	Ernesto S. Nakayasu
title	Ancient Regulatory Role of Lysine Acetylation in Central Metabolism
title_short	Ancient Regulatory Role of Lysine Acetylation in Central Metabolism
title_full	Ancient Regulatory Role of Lysine Acetylation in Central Metabolism
title_fullStr	Ancient Regulatory Role of Lysine Acetylation in Central Metabolism
title_full_unstemmed	Ancient Regulatory Role of Lysine Acetylation in Central Metabolism
title_sort	ancient regulatory role of lysine acetylation in central metabolism
publisher	American Society for Microbiology
publishDate	2017
url	https://doaj.org/article/3609a2a8164d44b5be96efbb71d34c8d
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Ancient Regulatory Role of Lysine Acetylation in Central Metabolism

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