Article

N−Lysine Acetylation of a Bacterial Transcription Factor Inhibits Its DNA-Binding Activity

Baylor College of Medicine, United States of America
PLoS ONE (Impact Factor: 3.53). 12/2010; 5(12):e15123. DOI: 10.1371/journal.pone.0015123
Source: PubMed

ABSTRACT Evidence suggesting that eukaryotes and archaea use reversible N(ε)-lysine (N(ε)-Lys) acetylation to modulate gene expression has been reported, but evidence for bacterial use of N(ε)-Lys acetylation for this purpose is lacking. Here, we report data in support of the notion that bacteria can control gene expression by modulating the acetylation state of transcription factors (TFs). We screened the E. coli proteome for substrates of the bacterial Gcn5-like protein acetyltransferase (Pat). Pat acetylated four TFs, including the RcsB global regulatory protein, which controls cell division, and capsule and flagellum biosynthesis in many bacteria. Pat acetylated residue Lys180 of RcsB, and the NAD(+)-dependent Sir2 (sirtuin)-like protein deacetylase (CobB) deacetylated acetylated RcsB (RcsB(Ac)), demonstrating that N(ε)-Lys acetylation of RcsB is reversible. Analysis of RcsB(Ac) and variant RcsB proteins carrying substitutions at Lys180 provided biochemical and physiological evidence implicating Lys180 as a critical residue for RcsB DNA-binding activity. These findings further the likelihood that reversible N(ε)-Lys acetylation of transcription factors is a mode of regulation of gene expression used by all cells.

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    • "In general, MS-based strategies allow the non-biased identification of a high number of targeted proteins/pathways. Other techniques , such as protein microarrays, have also been used for the identification of substrates of acetyltransferases, although in vitro specificities may not mirror what happens in vivo [47]. "
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    ABSTRACT: Post-translational modification of proteins is a reversible mechanism of cellular adaptation to changing environmental conditions. In eukaryotes, the physiological relevance of N-ɛ-lysine protein acetylation is well demonstrated. In recent times, important roles in the regulation of metabolic processes in bacteria are being uncovered, adding complexity to cellular regulatory networks. The aim of this mini-review is to sum up the current state-of-the-art in the regulation of bacterial physiology by protein acetylation. Current knowledge on the molecular biology aspects of known bacterial protein acetyltransferases and deacetylases will be summarized. Protein acetylation in Escherichia coli, Salmonella enterica, Bacillus subtilis, Rhodopseudomonas palustris and Mycobacterium tuberculosis, will be explained in the light of their physiological relevance. Progress in the elucidation of bacterial acetylomes and the emerging understanding of chemical acylation mechanisms will be discussed together with their regulatory and evolutionary implications. Fundamental molecular studies detailing this recently discovered regulatory mechanism pave the way for their prospective application for the construction of synthetic regulation networks.
    New Biotechnology 12/2014; 31(6). DOI:10.1016/j.nbt.2014.03.002 · 2.90 Impact Factor
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    • "Since then, reported applications of functional protein microarrays in basic research, as well as in clinical applications , have increased rapidly. Significant achievements in providing the whole proteome of several organisms (i.e., human, yeast, Escherichia coli, virus) on arrays have provided the tools for many important biological discoveries (Zhu and Snyder, 2001; Zhu et al., 2006; Zhu et al., 2009; Thao et al., 2010). Moreover , protein microarrays enable the study of many post-translational modifications (i.e., phosphorylation, acetylation, ubiquitylation, S-nitrosylation) in a large-scale fashion, which is critical for understanding cellular protein synthesis and function (Zhu et al., 2000; Lu et al., 2008; Foster et al., 2009; Lin et al., 2009). "
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    ABSTRACT: Protein microarray technology is an emerging field that provides a versatile platform for the characterization of hundreds of thousands of proteins in a highly parallel and high-throughput manner. Protein microarrays are composed of two major classes: analytical and functional. In addition, tissue or cell lysates can also be fractionated and spotted on a slide to form a reverse-phase protein microarray. Applications of protein microarrays, especially functional protein microarrays, have flourished over the past decade as the fabrication technology has matured. In this unit, advances in protein microarray technologies are reviewed, and then a series of examples are presented to illustrate the applications of analytical and functional protein microarrays in both basic and clinical research. Relevant areas of research include the detection of various binding properties of proteins, the study of protein post-translational modifications, the analysis of host-microbe interactions, profiling antibody specificity, and the identification of biomarkers in autoimmune diseases.
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    • "Since then, reported applications of functional protein microarrays in basic research, as well as in clinical applications , have increased rapidly. Significant achievements in providing the whole proteome of several organisms (i.e., human, yeast, Escherichia coli, virus) on arrays have provided the tools for many important biological discoveries (Zhu and Snyder, 2001; Zhu et al., 2006; Zhu et al., 2009; Thao et al., 2010). Moreover , protein microarrays enable the study of many post-translational modifications (i.e., phosphorylation, acetylation, ubiquitylation, S-nitrosylation) in a large-scale fashion, which is critical for understanding cellular protein synthesis and function (Zhu et al., 2000; Lu et al., 2008; Foster et al., 2009; Lin et al., 2009). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Protein microarray technology is an emerging field that provides a versatile platform for the characterization of hundreds of thousands of proteins in a highly parallel and high-throughput manner. Protein microarrays are composed of two major classes: analytical and functional. In addition, tissue or cell lysates can also be fractionated and spotted on a slide to form a reverse-phase protein microarray. Applications of protein microarrays, especially functional protein microarrays, have flourished over the past decade as the fabrication technology has matured. In this unit, advances in protein microarray technologies are reviewed, and then a series of examples are presented to illustrate the applications of analytical and functional protein microarrays in both basic and clinical research. Relevant areas of research include the detection of various binding properties of proteins, the study of protein post-translational modifications, the analysis of host-microbe interactions, profiling antibody specificity, and the identification of biomarkers in autoimmune diseases. Curr. Protoc. Protein Sci. 72:27.1.1-27.1.16. © 2013 by John Wiley & Sons, Inc.
    Current protocols in protein science / editorial board, John E. Coligan ... [et al.] 04/2013; Chapter 27:Unit27.1.
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