Identification of arginine- and lysine-methylation in the proteome of Saccharomyces cerevisiae and its functional implications

Chi Nam Ignatius Pang,Marc R Wilkins,Elisabeth Gasteiger

doi:10.1186/1471-2164-11-92

Chi Nam Ignatius Pang, Marc R Wilkins + Show 1 more

Open Access

https://doi.org/10.1186/1471-2164-11-92

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Abstract

BackgroundThe methylation of eukaryotic proteins has been proposed to be widespread, but this has not been conclusively shown to date. In this study, we examined 36,854 previously generated peptide mass spectra from 2,607 Saccharomyces cerevisiae proteins for the presence of arginine and lysine methylation. This was done using the FindMod tool and 5 filters that took advantage of the high number of replicate analysis per protein and the presence of overlapping peptides.ResultsA total of 83 high-confidence lysine and arginine methylation sites were found in 66 proteins. Motif analysis revealed many methylated sites were associated with MK, RGG/RXG/RGX or WXXXR motifs. Functionally, methylated proteins were significantly enriched for protein translation, ribosomal biogenesis and assembly and organellar organisation and were predominantly found in the cytoplasm and ribosome. Intriguingly, methylated proteins were seen to have significantly longer half-life than proteins for which no methylation was found. Some 43% of methylated lysine sites were predicted to be amenable to ubiquitination, suggesting methyl-lysine might block the action of ubiquitin ligase.ConclusionsThis study suggests protein methylation to be quite widespread, albeit associated with specific functions. Large-scale tandem mass spectroscopy analyses will help to further confirm the modifications reported here.

Highlights

The methylation of eukaryotic proteins has been proposed to be widespread, but this has not been conclusively shown to date
For the peptide to be included in the final set of methylated peptides, at least one peptide in the overlapping peptides had to be an unambiguous peptide match
This study is a step towards the definition of the methyl proteome of S. cerevisiae

Summary

Introduction

The methylation of eukaryotic proteins has been proposed to be widespread, but this has not been conclusively shown to date. We examined 36,854 previously generated peptide mass spectra from 2,607 Saccharomyces cerevisiae proteins for the presence of arginine and lysine methylation. This was done using the FindMod tool and 5 filters that took advantage of the high number of replicate analysis per protein and the presence of overlapping peptides. The methylation of proteins is of increasing biological interest. It is predominantly found on lysine and arginine residues, but has been found on histidine, glutamic acid and on the carboxyl groups of proteins (reviewed in Grillo and Colombatto 2005) [1].

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