Abstract
Protein N-terminal acetylation is a co- and posttranslational modification, conserved among eukaryotes. It determines the functional fate of many proteins including their stability, complex formation, and subcellular localization. N-terminal acetyltransferases (NATs) transfer an acetyl group to the N-termini of proteins, and the major NATs in yeast and humans are NatA, NatB, and NatC. In this study, we characterized the Trypanosoma cruzi (T. cruzi) NatC and NatA protein complexes, each consisting of one catalytic subunit and predicted auxiliary subunits. The proteins were found to be expressed in the three main life cycle stages of the parasite, formed stable complexes in vivo, and partially cosedimented with the ribosome in agreement with a cotranslational function. An in vitro acetylation assay clearly demonstrated that the acetylated substrates of the NatC catalytic subunit from T. cruzi were similar to those of yeast and human NatC, suggesting evolutionary conservation of function. An RNAi knockdown of the Trypanosoma brucei (T. brucei) NatC catalytic subunit indicated that reduced NatC-mediated N-terminal acetylation of target proteins reduces parasite growth.
Highlights
Trypanosomes are protozoan parasites that can cause severe health problems, mainly in developing countries
We find that TcNaa30 catalyzes the acetylation of N-termini similar to those acetylated by NatC in yeast and hNaa30 in vitro and our analyses indicate that the protein may function both as a Nα- and as a Nε-acetyltransferase
The catalytic subunit of the TcNatC complex was identified by blast analysis and as previously described [19] (Table 1)
Summary
Trypanosomes are protozoan parasites that can cause severe health problems, mainly in developing countries. Trypanosoma cruzi is the causative agent of Chagas disease, common throughout Latin America, while T. brucei, mainly present in Africa, causes sleeping sickness in humans and Nagana in livestock [1, 2]. There is no vaccine against trypanosome-related diseases and the available drugs cause serious side effects [3, 4]. Protein Nα-acetylation (Nt-acetylation) is an irreversible protein modification where the acetyl moiety is transferred to the Nα amino group of a protein or polypeptide by N-terminal acetyltransferases (NATs). NATs are grouped according to their substrate specificity. Seven NATs have been identified so far (NatA-F and NatH) [5, 6]. NatA, NatB, and NatC have the largest number
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