YcgC represents a new protein deacetylase family in prokaryotes

Abstract

Reversible lysine acetylation is one of the most important protein posttranslational modifications that plays essential roles in both prokaryotes and eukaryotes. However, only a few lysine deacetylases (KDACs) have been identified in prokaryotes, perhaps in part due to their limited sequence homology. Herein, we developed a ‘clip-chip’ strategy to enable unbiased, activity-based discovery of novel KDACs in the Escherichia coli proteome. In-depth biochemical characterization confirmed that YcgC is a serine hydrolase involving Ser200 as the catalytic nucleophile for lysine deacetylation and does not use NAD+ or Zn2+ like other established KDACs. Further, in vivo characterization demonstrated that YcgC regulates transcription by catalyzing deacetylation of Lys52 and Lys62 of a transcriptional repressor RutR. Importantly, YcgC targets a distinct set of substrates from the only known E. coli KDAC CobB. Analysis of YcgC’s bacterial homologs confirmed that they also exhibit KDAC activity. YcgC thus represents a novel family of prokaryotic KDACs.DOI: http://dx.doi.org/10.7554/eLife.05322.001

Lysine acetylation regulates the activity of <italic>Escherichia coli</italic> S-adenosylmethionine synthase

“…In addition, we noticed that even after long periods of CobB treatment, deacetylation of Ac-MAT was still incomplete, as shown by western blot analysis and LC-MS analysis. A possible explanation may be that CobB is not the only deacetylase that exhibits lysine deacetylase (KDAC) activity [61].…”

Regulation, Function, and Detection of Protein Acetylation in Bacteria

“…If we find acetylation occupancy to be high at a particular site, the likelihood of an inherently slow nonenzymatic mechanism may be diminished and may therefore suggest enzymatic acetylation. With a large number of acetylated proteins, it seems probable that more enzymes exist, and new ones continue to be discovered in both bacteria (61,67) and mitochondria (140). Answering these questions is important in moving toward an understanding of the biological significance of protein acetylation in bacteria.…”

The unexpected complexity of bacterial genomes

“…In enterotoxigenic E. coli, the transcription factor CRP activates a promoter (bent arrow) between convergent genes (beige block arrows) to control expression of an unannotated gene (blue block arrow) (Haycocks & Grainger, 2016). (b) In E. coli K-12, the transcriptional repressor RutR binds within genes and prevents their expression (Shimada et al, 2008;Tu et al, 2015). (c) An M. tuberculosis operon contains an internal promoter that is activated by CRP (Knapp et al, 2015).…”

“…Initial inspection detected RutR-mediated repression at only one such target; expression of ves was undetectable in the presence of RutR (Shimada et al 2008). However, subsequent work has shown that RutR activity is controlled by deacetylation and autoproteolysis (Tu et al, 2015). Thus, under appropriate conditions, repression of further RutR target genes is apparent.…”