title: Cross-talk between phosphorylation and lysine acetylation in a genome-reduced bacterium.
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.
authors.affiliation: Structural and Computational Biology Unit, European Molecular Biology Laboratory, EMBL, Heidelberg, Germany.
authors.forename: Vera
authors.initials: V
authors.lastname: van Noort
authors.forename: Jan
authors.initials: J
authors.lastname: Seebacher
authors.forename: Samuel
authors.initials: S
authors.lastname: Bader
authors.forename: Shabaz
authors.initials: S
authors.lastname: Mohammed
authors.forename: Ivana
authors.initials: I
authors.lastname: Vonkova
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Betts
authors.forename: Sebastian
authors.initials: S
authors.lastname: Kühner
authors.forename: Runjun
authors.initials: R
authors.lastname: Kumar
authors.forename: Tobias
authors.initials: T
authors.lastname: Maier
authors.forename: Martina
authors.initials: M
authors.lastname: O'Flaherty
authors.forename: Vladimir
authors.initials: V
authors.lastname: Rybin
authors.forename: Arne
authors.initials: A
authors.lastname: Schmeisky
authors.forename: Eva
authors.initials: E
authors.lastname: Yus
authors.forename: Jörg
authors.initials: J
authors.lastname: Stülke
authors.forename: Luis
authors.initials: L
authors.lastname: Serrano
authors.forename: Robert B
authors.initials: RB
authors.lastname: Russell
authors.forename: Albert J R
authors.initials: AJ
authors.lastname: Heck
authors.forename: Peer
authors.initials: P
authors.lastname: Bork
authors.forename: Anne-Claude
authors.initials: AC
authors.lastname: Gavin
mesh_terms: D000107:Acetylation; D000115:Acetylesterase / Q000378:metabolism*; D020134:Catalytic Domain / Q000235:genetics; D019143:Evolution, Molecular; D053263:Gene Regulatory Networks / Q000235:genetics / Q000502:physiology; D059646:Genome Size / Q000235:genetics*; D016680:Genome, Bacterial / Q000235:genetics; D008239:Lysine / Q000378:metabolism*; D053858:Metabolic Networks and Pathways / Q000235:genetics* / Q000502:physiology; D008954:Models, Biological; D030781:Organisms, Genetically Modified; D010766:Phosphorylation / Q000502:physiology; D011019:Pneumonia, Mycoplasma / Q000235:genetics* / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism*; D011499:Protein Processing, Post-Translational / Q000235:genetics; D020543:Proteome / Q000235:genetics / Q000378:metabolism
chemical_list: D020543:Proteome; D011494:Protein Kinases; D000115:Acetylesterase; D008239:Lysine