Characterization of Evolutionarily Conserved Trypanosoma cruzi NatC and NatA-N-Terminal Acetyltransferase Complexes

Article Authors: Stephen Ochaya, Oscar Franzén, Doreen Asiimwe Buhwa, Håvard Foyn, Claire E Butler, Svein Isungset Stove, Kevin M Tyler, Thomas Arnesen, Enock Matovu, Lena Åslund 8, Björn Andersson

    • 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.

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    DOI https://doi.org/10.1155/2019/6594212
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    Affiliation
    • 1Department of Cell and Molecular Biology, Karolinska Institutet, Box 285, 171 77 Stockholm, Sweden.
    • 2Department of Immunology and Microbiology, Gulu University, P.O. Box, 166 Gulu, Uganda.
    • 3Department of Parasitology and Microbiology, Makerere University, P.O. Box 7062, Kampala, Uganda.
    • 4Department of Biological Sciences, University of Bergen, N-5020 Bergen, Norway.
    • 5Biomedical Research Centre, Norwich Medical School, University of East Anglia, Norwich, Norfolk, NR4 7TJ, UK.
    • 6Department of Biomedicine, University of Bergen, 5020 Bergen, Norway.
    • 7Department of Surgery, Haukeland University Hospital, N-5020 Bergen, Norway.
    • 8Department of Immunology, Genetics and Pathology, Rudbeck Laboratory, 75185 Uppsala, Sweden.