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.; Msadek, Tarek

doi:10.1128/mBio.01894-17

Ancient Regulatory Role of Lysine Acetylation in Central Metabolism

Journal Article · Tue Nov 28 04:00:00 EST 2017 · mBio (Online)

DOI:https://doi.org/10.1128/mBio.01894-17· OSTI ID:1439706

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, Tarek

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.

IMPORTANCEPost-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.

Research Organization:: Pacific Northwest National Laboratory (PNNL), Richland, WA (US), Environmental Molecular Sciences Laboratory (EMSL)

Sponsoring Organization:: USDOE

DOE Contract Number:: AC05-76RL01830

OSTI ID:: 1439706

Report Number(s):: PNNL-SA-124565; 48582; KP1601010

Journal Information:: mBio (Online), Journal Name: mBio (Online) Journal Issue: 6 Vol. 8; ISSN 2150-7511

Publisher:: American Society for Microbiology

Country of Publication:: United States

Language:: English

References (39)

Protein lysine acetylation in bacteria: Current state of the art Ouidir, Tassadit; Kentache, Takfarinas; Hardouin, Julie PROTEOMICS, Vol. 16, Issue 2 https://doi.org/10.1002/pmic.201500258	journal	December 2015
Lysine Acetylation Targets Protein Complexes and Co-Regulates Major Cellular Functions Choudhary, C.; Kumar, C.; Gnad, F. Science, Vol. 325, Issue 5942 https://doi.org/10.1126/science.1175371	journal	July 2009
Structural and Functional Studies Suggest a Catalytic Mechanism for the Phosphotransacetylase from Methanosarcina thermophila Lawrence, S. H.; Luther, K. B.; Schindelin, H. Journal of Bacteriology, Vol. 188, Issue 3 https://doi.org/10.1128/JB.188.3.1143-1154.2006	journal	January 2006
Histoplasmosis in HIV-Infected Patients: A Review of New Developments and Remaining Gaps Adenis, Antoine A.; Aznar, Christine; Couppié, Pierre Current Tropical Medicine Reports https://doi.org/10.1007/s40475-014-0017-8	journal	March 2014
Mechanistic implications for Escherichia coli cofactor-dependent phosphoglycerate mutase based on the high-resolution crystal structure of a vanadate complex Bond, Charles S.; White, Malcolm F.; Hunter, William N. Journal of Molecular Biology, Vol. 316, Issue 5 https://doi.org/10.1006/jmbi.2002.5418	journal	March 2002
BlastKOALA and GhostKOALA: KEGG Tools for Functional Characterization of Genome and Metagenome Sequences Kanehisa, Minoru; Sato, Yoko; Morishima, Kanae Journal of Molecular Biology, Vol. 428, Issue 4 https://doi.org/10.1016/j.jmb.2015.11.006	journal	February 2016
The 1.75 Å Crystal Structure of Acetyl-CoA Synthetase Bound to Adenosine-5‘-propylphosphate and Coenzyme A ^† Gulick, Andrew M.; Starai, Vincent J.; Horswill, Alexander R. Biochemistry, Vol. 42, Issue 10, p. 2866-2873 https://doi.org/10.1021/bi0271603	journal	March 2003
Protein acetylation dynamics in response to carbon overflow in E scherichia coli : Acetylation dynamics and overflow metabolism Schilling, Birgit; Christensen, David; Davis, Robert Molecular Microbiology, Vol. 98, Issue 5 https://doi.org/10.1111/mmi.13161	journal	September 2015
The Intracellular Concentration of Acetyl Phosphate in Escherichia coli Is Sufficient for Direct Phosphorylation of Two-Component Response Regulators Klein, A. H.; Shulla, A.; Reimann, S. A. Journal of Bacteriology, Vol. 189, Issue 15 https://doi.org/10.1128/JB.00564-07	journal	June 2007
CASTp: Computed Atlas of Surface Topography of proteins Binkowski, T. A. Nucleic Acids Research, Vol. 31, Issue 13 https://doi.org/10.1093/nar/gkg512	journal	July 2003
Evolution of protein phosphorylation across 18 fungal species Studer, R. A.; Rodriguez-Mias, R. A.; Haas, K. M. Science, Vol. 354, Issue 6309 https://doi.org/10.1126/science.aaf2144	journal	October 2016
Crystal structures of putative phosphoglycerate kinases from B. anthracis and C. jejuni Zheng, Heping; Filippova, Ekaterina V.; Tkaczuk, Karolina L. Journal of Structural and Functional Genomics, Vol. 13, Issue 1 https://doi.org/10.1007/s10969-012-9131-9	journal	March 2012
The multisubunit active site of fumarase C from Escherichia coli Weaver, T. M.; Levitt, D. G.; Donnelly, M. I. Nature Structural Biology, Vol. 2, Issue 8 https://doi.org/10.1038/nsb0895-654	journal	August 1995
Analysis Tool Web Services from the EMBL-EBI McWilliam, Hamish; Li, Weizhong; Uludag, Mahmut Nucleic Acids Research, Vol. 41, Issue W1 https://doi.org/10.1093/nar/gkt376	journal	May 2013
Cellular Stoichiometry of the Chemotaxis Proteins in Bacillus subtilis Cannistraro, V. J.; Glekas, G. D.; Rao, C. V. Journal of Bacteriology, Vol. 193, Issue 13 https://doi.org/10.1128/JB.01255-10	journal	April 2011
Regulation of Cellular Metabolism by Protein Lysine Acetylation Zhao, S.; Xu, W.; Jiang, W. Science, Vol. 327, Issue 5968 https://doi.org/10.1126/science.1179689	journal	February 2010
Structural, Kinetic and Proteomic Characterization of Acetyl Phosphate-Dependent Bacterial Protein Acetylation Kuhn, Misty L.; Zemaitaitis, Bozena; Hu, Linda I. PLoS ONE, Vol. 9, Issue 4 https://doi.org/10.1371/journal.pone.0094816	journal	April 2014
Correcting systematic bias and instrument measurement drift with mzRefinery: Fig. 1. Gibbons, Bryson C.; Chambers, Matthew C.; Monroe, Matthew E. Bioinformatics https://doi.org/10.1093/bioinformatics/btv437	journal	August 2015
Refined crystal structure of lipoamide dehydrogenase from Azotobacter vinelandii at 2.2 Å resolution Mattevi, Andrea; Schierbeek, Abraham J.; Hol, Wim G. J. Journal of Molecular Biology, Vol. 220, Issue 4 https://doi.org/10.1016/0022-2836(91)90367-F	journal	August 1991
A Skyline Plugin for Pathway-Centric Data Browsing Degan, Michael G.; Ryadinskiy, Lillian; Fujimoto, Grant M. Journal of The American Society for Mass Spectrometry, Vol. 27, Issue 11 https://doi.org/10.1007/s13361-016-1448-3	journal	August 2016
mzML: A single, unifying data format for mass spectrometer output Deutsch, Eric PROTEOMICS, Vol. 8, Issue 14 https://doi.org/10.1002/pmic.200890049	journal	July 2008
Structural studies of phosphoglucose isomerase from Mycobacterium tuberculosis H37Rv Anand, Kanchan; Mathur, Divya; Anant, Avishek Acta Crystallographica Section F Structural Biology and Crystallization Communications, Vol. 66, Issue 5 https://doi.org/10.1107/S1744309110011656	journal	April 2010
Genes essential for phototrophic growth by a purple alphaproteobacterium: Genes for phototrophic growth Yang, Jianming; Yin, Liang; Lessner, Faith H. Environmental Microbiology, Vol. 19, Issue 9 https://doi.org/10.1111/1462-2920.13852	journal	July 2017
The crystal structure of Escherichia coli class II fructose-1,6-bisphosphate aldolase in complex with phosphoglycolohydroxamate reveals details of mechanism and specificity 1 1Edited by R. Huber Hall, David R.; Leonard, Gordon A.; Reed, Christopher D. Journal of Molecular Biology, Vol. 287, Issue 2 https://doi.org/10.1006/jmbi.1999.2609	journal	March 1999
Triosephosphate Isomerase Requires a Positively Charged Active Site: The Role of Lysine-12 Lodi, Patricia J.; Chang, Louise C.; Knowles, Jeremy R. Biochemistry, Vol. 33, Issue 10 https://doi.org/10.1021/bi00176a009	journal	March 1994
MUSCLE: multiple sequence alignment with high accuracy and high throughput Edgar, R. C. Nucleic Acids Research, Vol. 32, Issue 5, p. 1792-1797 https://doi.org/10.1093/nar/gkh340	journal	March 2004
Mechanism of enolase: the crystal structure of enolase-magnesium-2-phosphoglycerate/phosphoenolpyruvate complex at 2.2-.ANG. resolution Lebioda, Lukasz; Stec, Boguslaw Biochemistry, Vol. 30, Issue 11 https://doi.org/10.1021/bi00225a012	journal	March 1991
Regulation of acetyl phosphate synthesis and degradation, and the control of flagellar expression in Escherichia coli Prüβ, Birgtt M.; Wolfe, Alan J. Molecular Microbiology, Vol. 12, Issue 6 https://doi.org/10.1111/j.1365-2958.1994.tb01085.x	journal	June 1994
The Acetate Switch Wolfe, Alan Microbiology and Molecular Biology Reviews, Vol. 69, Issue 1, p. 12-50 https://doi.org/10.1128/MMBR.69.1.12-50.2005	journal	March 2005
Sir2-Dependent Activation of Acetyl-CoA Synthetase by Deacetylation of Active Lysine Starai, V. J.; Celic, I.; Cole, R. N. Science, Vol. 298, Issue 5602, p. 2390-2392 https://doi.org/10.1126/science.1077650	journal	December 2002
The allosteric regulation of pyruvate kinase by fructose-1,6-bisphosphate Jurica, Melissa S.; Mesecar, Andrew; Heath, Patrick J. Structure, Vol. 6, Issue 2 https://doi.org/10.1016/S0969-2126(98)00021-5	journal	February 1998
Acetyl-Phosphate Is a Critical Determinant of Lysine Acetylation in E. coli Weinert, Brian T.; Iesmantavicius, Vytautas; Wagner, Sebastian A. Molecular Cell, Vol. 51, Issue 2 https://doi.org/10.1016/j.molcel.2013.06.003	journal	July 2013
Oxidative Stress Activates SIRT2 to Deacetylate and Stimulate Phosphoglycerate Mutase Xu, Y.; Li, F.; Lv, L. Cancer Research, Vol. 74, Issue 13 https://doi.org/10.1158/0008-5472.CAN-13-3615	journal	May 2014
ADP-Binding Site of Escherichia coli Succinyl-CoA Synthetase Revealed by X-ray Crystallography ^† ^, ^‡ Joyce, Michael A.; Fraser, Marie E.; James, Michael N. G. Biochemistry, Vol. 39, Issue 1 https://doi.org/10.1021/bi991696f	journal	January 2000
ProteoWizard: open source software for rapid proteomics tools development Kessner, Darren; Chambers, Matt; Burke, Robert Bioinformatics, Vol. 24, Issue 21 https://doi.org/10.1093/bioinformatics/btn323	journal	July 2008
On the origin of biochemistry at an alkaline hydrothermal vent Martin, William; Russell, Michael J. Philosophical Transactions of the Royal Society B: Biological Sciences, Vol. 362, Issue 1486 https://doi.org/10.1098/rstb.2006.1881	journal	November 2006
Multicopy Single-Stranded DNA Directs Intestinal Colonization of Enteric Pathogens Elfenbein, Johanna R.; Knodler, Leigh A.; Nakayasu, Ernesto S. PLOS Genetics, Vol. 11, Issue 9 https://doi.org/10.1371/journal.pgen.1005472	journal	September 2015
ETE 3: Reconstruction, Analysis, and Visualization of Phylogenomic Data Huerta-Cepas, Jaime; Serra, François; Bork, Peer Molecular Biology and Evolution, Vol. 33, Issue 6 https://doi.org/10.1093/molbev/msw046	journal	February 2016
Crystal Structure of Bacillus subtilis Isocitrate Dehydrogenase at 1.55 Å : INSIGHTS INTO THE NATURE OF SUBSTRATE SPECIFICITY EXHIBITED BY Singh, Satinder K.; Matsuno, Kiyoshi; LaPorte, David C. Journal of Biological Chemistry, Vol. 276, Issue 28 https://doi.org/10.1074/jbc.M101191200	journal	April 2001

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