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

van Noort V, Seebacher J, Bader S, Mohammed S, Vonkova I, Betts MJ, Kühner S, Kumar R, Maier T, O'Flaherty M, Rybin V, Schmeisky A, Yus E, Stülke J, Serrano L, Russell RB, Heck AJ, Bork P, Gavin AC - Mol. Syst. Biol. (2012)

Bottom Line: 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.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.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.

View Article: PubMed Central - PubMed

Affiliation: Structural and Computational Biology Unit, European Molecular Biology Laboratory, EMBL, Heidelberg, Germany.

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.

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M. pneumoniae proteome, phosphoproteome and lysine acetylome. (A) Modified proteins are significantly enriched in functions related to metabolism and cellular processes and signaling. (B) Box plots indicating the relative extents of modification for serines, threonines, tyrosines and lysines within all observed modified proteins. (C) Modified proteins show a complex pattern of modification. Bubble plot showing the number of proteins with distinct modification profiles. (D) Phosphorylation is more positionally conserved in bacteria than lysine acetylation. The fraction of conserved modified residues is shown for either precise site conservation (site conservation) or a more plastic conservation within three residues (±1 amino acids conservation).
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f2: M. pneumoniae proteome, phosphoproteome and lysine acetylome. (A) Modified proteins are significantly enriched in functions related to metabolism and cellular processes and signaling. (B) Box plots indicating the relative extents of modification for serines, threonines, tyrosines and lysines within all observed modified proteins. (C) Modified proteins show a complex pattern of modification. Bubble plot showing the number of proteins with distinct modification profiles. (D) Phosphorylation is more positionally conserved in bacteria than lysine acetylation. The fraction of conserved modified residues is shown for either precise site conservation (site conservation) or a more plastic conservation within three residues (±1 amino acids conservation).

Mentions: The data set covers 81.6% of all annotated open reading frames (ORFs) or 93% of the previously identified M. pneumoniae proteome (Jaffe et al, 2004; Kuhner et al, 2009) (Supplementary Figure S1A). The sets of protein identified broadly cover all cellular functions (Figure 2A). The median sequence coverage of all identified proteins reaches 43%, a value close to the known upper detection limit inherent to current MS-based protocols (Supplementary Figure S1B) (Swaney et al, 2010). We tested the set for several possible biases, and found that the sets of proteins identified broadly cover all biophysical and biochemical properties (Supplementary Figure S3). Taken together, the data set is among the most comprehensive analyses of both phosphorylation and lysine acetylation in a single prokaryote. The results show that lysine acetylation in M. pneumoniae is very common, being at least as frequent as phosphorylation.


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

van Noort V, Seebacher J, Bader S, Mohammed S, Vonkova I, Betts MJ, Kühner S, Kumar R, Maier T, O'Flaherty M, Rybin V, Schmeisky A, Yus E, Stülke J, Serrano L, Russell RB, Heck AJ, Bork P, Gavin AC - Mol. Syst. Biol. (2012)

M. pneumoniae proteome, phosphoproteome and lysine acetylome. (A) Modified proteins are significantly enriched in functions related to metabolism and cellular processes and signaling. (B) Box plots indicating the relative extents of modification for serines, threonines, tyrosines and lysines within all observed modified proteins. (C) Modified proteins show a complex pattern of modification. Bubble plot showing the number of proteins with distinct modification profiles. (D) Phosphorylation is more positionally conserved in bacteria than lysine acetylation. The fraction of conserved modified residues is shown for either precise site conservation (site conservation) or a more plastic conservation within three residues (±1 amino acids conservation).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3293634&req=5

f2: M. pneumoniae proteome, phosphoproteome and lysine acetylome. (A) Modified proteins are significantly enriched in functions related to metabolism and cellular processes and signaling. (B) Box plots indicating the relative extents of modification for serines, threonines, tyrosines and lysines within all observed modified proteins. (C) Modified proteins show a complex pattern of modification. Bubble plot showing the number of proteins with distinct modification profiles. (D) Phosphorylation is more positionally conserved in bacteria than lysine acetylation. The fraction of conserved modified residues is shown for either precise site conservation (site conservation) or a more plastic conservation within three residues (±1 amino acids conservation).
Mentions: The data set covers 81.6% of all annotated open reading frames (ORFs) or 93% of the previously identified M. pneumoniae proteome (Jaffe et al, 2004; Kuhner et al, 2009) (Supplementary Figure S1A). The sets of protein identified broadly cover all cellular functions (Figure 2A). The median sequence coverage of all identified proteins reaches 43%, a value close to the known upper detection limit inherent to current MS-based protocols (Supplementary Figure S1B) (Swaney et al, 2010). We tested the set for several possible biases, and found that the sets of proteins identified broadly cover all biophysical and biochemical properties (Supplementary Figure S3). Taken together, the data set is among the most comprehensive analyses of both phosphorylation and lysine acetylation in a single prokaryote. The results show that lysine acetylation in M. pneumoniae is very common, being at least as frequent as phosphorylation.

Bottom Line: 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.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.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.

View Article: PubMed Central - PubMed

Affiliation: Structural and Computational Biology Unit, European Molecular Biology Laboratory, EMBL, Heidelberg, Germany.

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.

Show MeSH
Related in: MedlinePlus