ABSTRACT
Post-translational methylation of proteins, which occurs in arginines and lysines, modulates several biological processes at different levels of cell signaling. Recently, methylation has been demonstrated in the regulation beyond histones, for example, in the dynamics of protein-protein interaction and protein-nucleic acid. Mass spectrometry-based proteomics has allowed a large-scale identification of protein methylation - mainly in arginine residues-, in different organisms, including some trypanosomes. However, the presence and role of protein methylation in Trypanosoma cruzi, the etiologic agent of Chagas disease, has not yet been elucidated. In this work, we applied mass spectrometry and described the arginine and lysine methylproteome of T. cruzi. In epimastigotes, 1336 methylsites (657 methyl-arginines and 679 methyl-lysines) in 878 methylated proteins were identified by LC-MS/MS. Our functional and interaction analyzes show that protein methylation impacts different biological processes, with emphasis on translation. Separately, protein arginine methylation is related to oxireduction and carbohydrate metabolism, while lysine methylation impacts the protein synthesis. In addition, 50 methylated proteins have been previously described with phosphorylation sites in T. cruzi, represented by RNA binding proteins, sterol methyltransferase activity and calpain peptidases, indicating the possibility of crosstalk in the regulation of these proteinsThis work represents the first proteomic analysis of T. cruzi methylproteome and is the first to characterize lysine methylation in trypanosomatids. Collectively, these data inform about new fundamental biological aspects of this organism impacted by protein methylation, that can contribute to the identification of pathways and key pieces in the biology of this human pathogen. Keywords: Trypanosoma cruzi. Protein methylation. Proteomics. LC-MS/MS.
Biological significance Trypanosoma cruzi is a protozoan parasite that causes Chagas’ disease in humans and throughout its life cycle faces different environment changes. Protein methylation is an important post-translational modification by which cells respond and adapt to the environment. To understand the importance of protein methylation in T.cruzi biology, we applied a mass spectrometry-based proteomics (GeLC-MS/MS) and report the first proteomic analysis of both arginine and lysine methylproteome in T. cruzi, being the first large-scale characterization of lysine methylation in trypanosomes. Our data demonstrate that the methylation of proteins in T. cruzi is broad and impacts different cellular processes. This study represents a significant advance on the importance of protein methylation in trypanosomes.
Highlights
First methylproteome description of human parasite T. cruzi and first of lysine methylation in trypanosomes;
Protein arginine and lysine methylation is widely found in T. cruzi epimastigotes;
Different processes are impacted by protein methylaton in T. cruzi, mainly the protein synthesis;
50 methylated proteins have been previously described with phosphorylation sites in T. cruzi.
- Trypanosoma cruzi
- Protein methylation
- Proteomics
- LC-MS/MS
Competing Interest Statement
The authors have declared no competing interest.