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Journal of Bacteriology Aug 2017-Lysine acetylation is now recognized as an abundant posttranslational modification (PTM) that influences many essential biological pathways. Advancements in mass... (Review)
Review
-Lysine acetylation is now recognized as an abundant posttranslational modification (PTM) that influences many essential biological pathways. Advancements in mass spectrometry-based proteomics have led to the discovery that bacteria contain hundreds of acetylated proteins, contrary to the prior notion of acetylation events being rare in bacteria. Although the mechanisms that regulate protein acetylation are still not fully defined, it is understood that this modification is finely tuned via both enzymatic and nonenzymatic mechanisms. The opposing actions of Gcn5-related -acetyltransferases (GNATs) and deacetylases, including sirtuins, provide the enzymatic control of lysine acetylation. A nonenzymatic mechanism of acetylation has also been demonstrated and proven to be prominent in bacteria, as well as in mitochondria. The functional consequences of the vast majority of the identified acetylation sites remain unknown. From studies in mammalian systems, acetylation of critical lysine residues was shown to impact protein function by altering its structure, subcellular localization, and interactions. It is becoming apparent that the same diversity of functions can be found in bacteria. Here, we review current knowledge of the mechanisms and the functional consequences of acetylation in bacteria. Additionally, we discuss the methods available for detecting acetylation sites, including quantitative mass spectrometry-based methods, which promise to promote this field of research. We conclude with possible future directions and broader implications of the study of protein acetylation in bacteria.
Topics: Acetylation; Bacteria; Bacterial Proteins; Mass Spectrometry; Protein Processing, Post-Translational; Proteome
PubMed: 28439035
DOI: 10.1128/JB.00107-17 -
Nature Structural & Molecular Biology Oct 2019The bromodomain (BrD) is a conserved structural module found in chromatin- and transcription-associated proteins that acts as the primary reader for acetylated lysine... (Review)
Review
The bromodomain (BrD) is a conserved structural module found in chromatin- and transcription-associated proteins that acts as the primary reader for acetylated lysine residues. This basic activity endows BrD proteins with versatile functions in the regulation of protein-protein interactions mediating chromatin-templated gene transcription, DNA recombination, replication and repair. Consequently, BrD proteins are involved in the pathogenesis of numerous human diseases. In this Review, we highlight our current understanding of BrD biology, and discuss the latest development of small-molecule inhibitors targeting BrDs as emerging epigenetic therapies for cancer and inflammatory disorders.
Topics: Acetylation; Animals; Drug Discovery; Epigenesis, Genetic; Histone Code; Histones; Humans; Inflammation; Models, Molecular; Neoplasms; Protein Domains; Small Molecule Libraries; Transcription Factors
PubMed: 31582847
DOI: 10.1038/s41594-019-0309-8 -
BioEssays : News and Reviews in... Nov 2019The N-end rule denotes the relationship between the identity of the amino-terminal residue of a protein and its in vivo half-life. Since its discovery in 1986, the N-end... (Review)
Review
The N-end rule denotes the relationship between the identity of the amino-terminal residue of a protein and its in vivo half-life. Since its discovery in 1986, the N-end rule has generally been described by a defined set of rules for determining whether an amino-terminal residue is stabilizing or not. However, recent studies are revealing that this N-end rule (or N-degron concept) is less straightforward than previously appreciated. For instance, it is unveiled that N-terminal acetylation of N-terminal residues may create a degradation signal (Ac-degron) that promotes the degradation of target proteins. A recent high-throughput dissection of degrons in yeast proteins amino termini intriguingly suggested that the hydrophobicity of amino-terminal residues-but not the N-terminal acetylation status-may be the indispensable feature of amino-terminal degrons. Herein, these recent advances in N-terminal acetylation and the complexity of N-terminal degradation signals in the context of the N-degron pathway are analyzed.
Topics: Acetylation; Fungal Proteins; Humans; Proteolysis
PubMed: 31549739
DOI: 10.1002/bies.201800167 -
Applied Biochemistry and Biotechnology Oct 2023Non-histone protein acetylation is involved in key cellular processes both in eukaryotes and prokaryotes. Acetylation in bacteria is used to modify proteins involved in...
Non-histone protein acetylation is involved in key cellular processes both in eukaryotes and prokaryotes. Acetylation in bacteria is used to modify proteins involved in metabolism and allow the bacteria to adapt to their environment. TTE (Thermoanaerobacter tengcongensis) is an anaerobic, thermophilic saccharolytic bacterium that grows at extreme temperature range between 50 and 80 ℃. The annotated TTE proteome contains less than 3000 proteins. We analyzed the proteome and acetylome of TTE using 2DLC-MS/MS (2-dimensional liquid chromatography mass spectrum). We evaluated the ability of mass spectrometry technology to cover a relatively small proteome as much as possible. And we also observed wide spread of acetylation in TTE, which changed under different temperatures. A total of 2082 proteins were identified, which accounts for about 82% of the database. A total of 2050 (~ 98%) proteins were quantified in at least one culture condition and 1818 proteins were quantified in all 4 conditions. The result also consisted 3457 acetylation sites corresponding to 827 distinct proteins, which covered 40% of the proteins identified. Bioinformatics analysis reported that proteins related to replication, recombination, repair, and extracellular structure cell wall biogenesis had more than half members acetylated, while energy production, carbohydrate transport, and metabolism related proteins were least acetylated. Our result suggested that acetylation affects the ATP-related energy metabolism and energy-dependent biosynthesis process. Comparing the enzymes related with lysine acetylation and acetyl-CoA (acetyl-coenzyme A) metabolism, we suggested that the acetylation of TTE took a non-enzymatic mechanism and affected by abundance of acetyl-CoA.
Topics: Proteome; Tandem Mass Spectrometry; Acetyl Coenzyme A; Acetylation; Protein Processing, Post-Translational
PubMed: 36809429
DOI: 10.1007/s12010-023-04361-9 -
Chemical Reviews Feb 2018
Topics: Acetylation; Methylation; Phosphorylation; Protein Processing, Post-Translational; Proteins
PubMed: 29439579
DOI: 10.1021/acs.chemrev.7b00756 -
Journal of Cellular Biochemistry Apr 2022Acetylation of proteins seems a widespread process found in the three domains of life. Several studies have shown that besides histones, acetylation of lysine residues... (Review)
Review
Acetylation of proteins seems a widespread process found in the three domains of life. Several studies have shown that besides histones, acetylation of lysine residues also occurs in non-nuclear proteins. Hence, it has been suggested that this covalent modification is a mechanism that might regulate diverse metabolic pathways by modulating enzyme activity, stability, and/or subcellular localization or interaction with other proteins. However, protein acetylation levels seem to have low correlation with modification of enzyme activity and pathway fluxes. In addition, the results obtained with mutant enzymes that presumably mimic acetylation have frequently been over-interpreted. Moreover, there is a generalized lack of rigorous enzyme kinetic analysis in parallel to acetylation level determinations. The purpose of this review is to analyze the current findings on the impact of acetylation on metabolic enzymes and its repercussion on metabolic pathways function/regulation.
Topics: Acetylation; Histones; Kinetics; Metabolic Networks and Pathways; Protein Processing, Post-Translational
PubMed: 34931340
DOI: 10.1002/jcb.30197 -
Chemistry & Biodiversity Jul 2023Grapefruit peel polysaccharide has antioxidant, antitumor, hypoglycemic and other biological activities, and chemical modification can further improve the properties of...
Grapefruit peel polysaccharide has antioxidant, antitumor, hypoglycemic and other biological activities, and chemical modification can further improve the properties of the polysaccharide. Acetylation modification of polysaccharides has the advantages of simple operation, low cost and little pollution, and is widely used at present. Different degrees of acetylation modification have different effects on the properties of polysaccharides, so it is necessary to optimize the preparation technology of acetylated grapefruit peel polysaccharides. In this article, acetylated grapefruit peel polysaccharide was prepared by acetic anhydride method. With the degree of acetyl substitution as the evaluation index, combined with the analysis of sugar content and protein content in the polysaccharide before and after modification, the effects of three feeding ratios of 1:0.6, 1 : 1.2 and 1 : 1.8 (polysaccharide: acetic anhydride, mass/volume) on acetylation modification were explored through single factor experiments. The results showed that the optimum ratio of material to liquid for acetylation modification of grapefruit peel polysaccharide was 1:0.6. Under these conditions, the degree of substitution of acetylated grapefruit peel polysaccharide was 0.323, the sugar content was 59.50 % and the protein content was 1.038 %. The results provide some reference for the study of acetylated grapefruit peel polysaccharide.
Topics: Citrus paradisi; Acetic Anhydrides; Polysaccharides; Sugars; Acetylation
PubMed: 37211951
DOI: 10.1002/cbdv.202300167 -
Genes & Development Apr 2018Fluctuations in acetyl-coenzyme A (acetyl-CoA) levels have been previously associated with changes in global histone acetylation and gene expression. The study by Lee... (Review)
Review
Fluctuations in acetyl-coenzyme A (acetyl-CoA) levels have been previously associated with changes in global histone acetylation and gene expression. The study by Lee and colleagues (pp. 497-511) in this issue of demonstrates that acetyl-CoA can promote the up-regulation of cell migration- and adhesion-related genes in glioblastoma by controlling Ca-NFAT (nuclear factor of activated T cells) signaling.
Topics: Acetyl Coenzyme A; Acetylation; Adult; Calcium; Cell Adhesion; Glioblastoma; Histones; Humans; Transcription, Genetic
PubMed: 29692354
DOI: 10.1101/gad.315168.118 -
Biochemical Society Transactions Dec 2021The dynamic processes of mitochondrial fusion and fission determine the shape of mitochondria, which can range from individual fragments to a hyperfused network, and... (Review)
Review
The dynamic processes of mitochondrial fusion and fission determine the shape of mitochondria, which can range from individual fragments to a hyperfused network, and influence mitochondrial function. Changes in mitochondrial shape can occur rapidly, allowing mitochondria to adapt to specific cues and changing cellular demands. Here, we will review what is known about how key proteins required for mitochondrial fusion and fission are regulated by their acetylation status, with acetylation promoting fission and deacetylation enhancing fusion. In particular, we will examine the roles of NAD+ dependant sirtuin deacetylases, which mediate mitochondrial acetylation, and how this post-translational modification provides an exquisite regulatory mechanism to co-ordinate mitochondrial function with metabolic demands of the cell.
Topics: Acetylation; Mitochondria; Mitochondrial Dynamics; Proteins
PubMed: 34812890
DOI: 10.1042/BST20210798 -
Expert Review of Proteomics Nov 2021Lysine acetylation is a reversible post-translational modification (PTM) regulated through the action of specific types of enzymes: lysine acetyltransferases (KATs) and... (Review)
Review
INTRODUCTION
Lysine acetylation is a reversible post-translational modification (PTM) regulated through the action of specific types of enzymes: lysine acetyltransferases (KATs) and lysine deacetylases (HDACs), in addition to bromodomains, which are a group of conserved domains which identify acetylated lysine residues, several of the players in the process of protein acetylation, including enzymes and bromodomain-containing proteins, have been related to the progression of several diseases. The combination of high-resolution mass spectrometry-based proteomics, and immunoprecipitation to enrich acetylated peptides has contributed in recent years to expand the knowledge about this PTM described initially in histones and nuclear proteins, and is currently reported in more than 5000 human proteins, that are regulated by this PTM.
AREAS COVERED
This review presents an overview of the main participant elements, the scenario in the development of protein lysine acetylation, and its role in different human pathologies.
EXPERT OPINION
Acetylation targets are practically all cellular processes in eukaryotes and prokaryotes organisms. Consequently, this modification has been linked to many pathologies like cancer, viral infection, obesity, diabetes, cardiovascular, and nervous system-associated diseases, to mention a few relevant examples. Accordingly, some intermediate mediators in the acetylation process have been projected as therapeutic targets.
Topics: Acetylation; Histones; Humans; Lysine; Protein Processing, Post-Translational; Proteomics
PubMed: 34791964
DOI: 10.1080/14789450.2021.2007766