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

Noort, Vera van; 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 Pubull, Luis, 1982-; Russell, Robert B.; Heck, Albert J.R.; Bork, Peer; Gavin, Anne-Claude

doi:http://dx.doi.org/10.1038/msb.2012.4

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

Citation

van Noort V, Seebacher J, Bader S, Mohammed S, Vonkova I, Betts MJ et al. Cross-talk between phosphorylation and lysine acetylation in a genome-reduced bacterium. Mol Syst Biol. 2012; 8: 571. DOI: 10.1038/msb.2012.4

Abstract

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.