Caracterização do Metilproteoma de Trypanosoma cruzi

Post-translational methylation of proteins, which occurs in arginines and lysines, modulates various biological processes at different levels of cell signaling. Mass spectrometry based proteomics allowed the identification of methylarginines in Trypanosoma brucei, which were strongly related to fundamental processes such as RNA metabolism, protein trafficking and parasite pathogenesis. 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, the presence of the methylation/ demethylation machinery in T. cruzi was identified and the methylproteome of arginine and lysine residues was identified through LC-MS/MS. In epimastigotes, 878 methylated proteins and 1336 methylation sites (657 methylarginines and 679 methyl lysines) were identified. These proteins, for the most part, are involved in protein synthesis and amino acid metabolism. While arginine methylation is related to different processes such as oxireduction and carbohydrate metabolism, methylation in lysine directly impacts the translation process. In addition, the co-occurrence between methylation and phosphorylation was detected in 62 T. cruzi proteins. This 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 and can contribute to the identification of key pieces in the process of adaptation and infection by the parasite and, ultimately, indicating possible candidates for chemotherapeutic targets.