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Sci. Signal., 26 July 2011
Vol. 4, Issue 183, p. ra48
[DOI: 10.1126/scisignal.2001902]

RESEARCH ARTICLES

Proteome-Wide Mapping of the Drosophila Acetylome Demonstrates a High Degree of Conservation of Lysine Acetylation

Brian T. Weinert1, Sebastian A. Wagner1, Heiko Horn2, Peter Henriksen1, Wenshe R. Liu3, Jesper V. Olsen1, Lars J. Jensen2, and Chunaram Choudhary1*

1 Department of Proteomics, The Novo Nordisk Foundation Center for Protein Research, Faculty of Health Sciences, University of Copenhagen, Blegdamsvej 3, 2200 Copenhagen, Denmark.
2 Department of Disease Systems Biology, The Novo Nordisk Foundation Center for Protein Research, Faculty of Health Sciences, University of Copenhagen, DK-2200 Copenhagen, Denmark.
3 Department of Chemistry, Texas A&M University, College Station, TX 77843, USA.

Abstract: Posttranslational modification of proteins by acetylation and phosphorylation regulates most cellular processes in living organisms. Surprisingly, the evolutionary conservation of phosphorylated serine and threonine residues is only marginally higher than that of unmodified serines and threonines. With high-resolution mass spectrometry, we identified 1981 lysine acetylation sites in the proteome of Drosophila melanogaster. We used data sets of experimentally identified acetylation and phosphorylation sites in Drosophila and humans to analyze the evolutionary conservation of these modification sites between flies and humans. Site-level conservation analysis revealed that acetylation sites are highly conserved, significantly more so than phosphorylation sites. Furthermore, comparison of lysine conservation in Drosophila and humans with that in nematodes and zebrafish revealed that acetylated lysines were significantly more conserved than were nonacetylated lysines. Bioinformatics analysis using Gene Ontology terms suggested that the proteins with conserved acetylation control cellular processes such as protein translation, protein folding, DNA packaging, and mitochondrial metabolism. We found that acetylation of ubiquitin-conjugating E2 enzymes was evolutionarily conserved, and mutation of a conserved acetylation site impaired the function of the human E2 enzyme UBE2D3. This systems-level analysis of comparative posttranslational modification showed that acetylation is an anciently conserved modification and suggests that phosphorylation sites may have evolved faster than acetylation sites.

* To whom correspondence should be addressed: E-mail: chuna.choudhary{at}cpr.ku.dk

Citation: B. T. Weinert, S. A. Wagner, H. Horn, P. Henriksen, W. R. Liu, J. V. Olsen, L. J. Jensen, C. Choudhary, Proteome-Wide Mapping of the Drosophila Acetylome Demonstrates a High Degree of Conservation of Lysine Acetylation. Sci. Signal. 4, ra48 (2011).

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