Cross‐talk between phosphorylation and lysine acetylation in a genome‐reduced bacterium

• Published in: Molecular systems biology Vol. 8; no. 1; pp. 571 - n/a
• Main Authors: van Noort, Vera, Seebacher, Jan, Bader, Samuel, Mohammed, Shabaz, Vonkova, Ivana, Betts, Matthew J, Kühner, Sebastian, Kumar, Runjun, Maier, Tobias, O'Flaherty, Martina, Rybin, Vladimir, Schmeisky, Arne, Yus, Eva, Stülke, Jörg, Serrano, Luis, Russell, Robert B, Heck, Albert JR, Bork, Peer, Gavin, Anne‐Claude
• Format: Journal Article
• Language: English
• Published: Chichester, UK John Wiley & Sons, Ltd 2012; EMBO Press; Nature Publishing Group
• Subjects: Acetylation; Acetylesterase - metabolism; Bacteria; Catalytic Domain - genetics; Clonal deletion; Eukaryotes; Evolution, Molecular; Gene expression; Gene regulation; Gene Regulatory Networks - genetics; Gene Regulatory Networks - physiology; Genome Size - genetics; Genome, Bacterial - genetics; Genomes; Genomics; Interfaces; kinase; Kinases; Lysine; Lysine - metabolism; Metabolic Networks and Pathways - genetics; Metabolic Networks and Pathways - physiology; Models, Biological; Mycoplasma pneumoniae; network; N‐acetyltransferase; Organisms, Genetically Modified; Peptides; Phosphatase; Phosphorylation; Phosphorylation - physiology; Pneumonia, Mycoplasma - genetics; Pneumonia, Mycoplasma - metabolism; post‐translational modification; Prokaryotes; Protein kinase; Protein Kinases - metabolism; Protein phosphatase; Protein Processing, Post-Translational - genetics; Proteins; Proteome - genetics; Proteome - metabolism; Proteomes; Proteomics; Regulatory mechanisms (biology); Transcription; Netherlands
• ISSN: 1744-4292; 1744-4292
• DOI: 10.1038/msb.2012.4

Protein post‐translational modifications (PTMs) represent important regulatory states that when combined have been hypothesized to act as molecular codes and to generate a functional diversity beyond genome and transcriptome. We systematically investigate the interplay of protein phosphorylation with other post‐transcriptional regulatory mechanisms in the genome‐reduced bacterium Mycoplasma pneumoniae. Systematic perturbations by deletion of its only two protein kinases and its unique protein phosphatase identified not only the protein‐specific effect on the phosphorylation network, but also a modulation of proteome abundance and lysine acetylation patterns, mostly in the absence of transcriptional changes. Reciprocally, deletion of the two putative N‐acetyltransferases affects protein phosphorylation, confirming cross‐talk between the two PTMs. The measured M. pneumoniae phosphoproteome and lysine acetylome revealed that both PTMs are very common, that (as in Eukaryotes) they often co‐occur within the same protein and that they are frequently observed at interaction interfaces and in multifunctional proteins. The results imply previously unreported hidden layers of post‐transcriptional regulation intertwining phosphorylation with lysine acetylation and other mechanisms that define the functional state of a cell. The effect of kinase, phosphatase and N‐acetyltransferase deletions on proteome phosphorylation and acetylation was investigated in Mycoplasma pneumoniae. Bi‐directional cross‐talk between post‐transcriptional modifications suggests an underlying regulatory molecular code in prokaryotes. Synopsis The effect of kinase, phosphatase and N‐acetyltransferase deletions on proteome phosphorylation and acetylation was investigated in Mycoplasma pneumoniae. Bi‐directional cross‐talk between post‐transcriptional modifications suggests an underlying regulatory molecular code in prokaryotes. Post‐translational modifications (PTMs) change the chemical properties of proteins, conferring diversity beyond the amino‐acid sequence. Proteins are often modified on multiple sites. A PTM code has been proposed, whereby modifications at specific positions influence further modifications. These regulatory circuits though have rarely been studied on a large‐scale; conservation in prokaryotes remains elusive. Here, we studied two important PTMs– phosphorylation and lysine acetylation in the small bacterium Mycoplasma pneumoniae. We combined genetics and quantitative mass spectrometry to measure the effect of systematic kinase, phosphatase and N‐acetyltransferase deletions on proteome abundance, phosphorylation and lysine acetylation. The data set represents a comprehensive analysis of both phosphorylation and lysine acetylation in a single prokaryote. It reveals (1) proteins often carry multiple modifications and multiple types of PTMs, reminiscent of the PTM code proposed in eukaryotes, (2) phosphorylation exerts pleiotropic effect on proteins abundances, phosphorylation, but also lysine acetylation, (3) the cross‐talk between the two PTMs is bi‐directional and (4) PTMs are frequently located at interaction interfaces and in multifunctional proteins, illustrating how PTMs could modulate protein functions affecting the way they interact. The study provides an unbiased and quantitative view on cross‐talk between phosphorylation and lysine acetylation. It suggests that these regulatory circuits are a fundamental principle of regulation that might have evolved before the divergence of prokaryotes and eukaryotes.