| Autor: |
Fragoso MSI; Instituto Carlos Chagas, Fundação Oswaldo Cruz, Curitiba 81350-010, Brazil., de Siqueira CM; Instituto Carlos Chagas, Fundação Oswaldo Cruz, Curitiba 81350-010, Brazil., Vitorino FNL; Special Laboratory of Cell Cycle, Center of Toxins, Immune Response and Cell Signalling (CeTICS), Instituto Butantan, São Paulo 05503-900, Brazil., Vieira AZ; Instituto Carlos Chagas, Fundação Oswaldo Cruz, Curitiba 81350-010, Brazil., Martins-Duarte ÉS; Department of Parasitology, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais, Belo Horizonte 31270-901, Brazil., Faoro H; Instituto Carlos Chagas, Fundação Oswaldo Cruz, Curitiba 81350-010, Brazil., da Cunha JPC; Special Laboratory of Cell Cycle, Center of Toxins, Immune Response and Cell Signalling (CeTICS), Instituto Butantan, São Paulo 05503-900, Brazil., Ávila AR; Instituto Carlos Chagas, Fundação Oswaldo Cruz, Curitiba 81350-010, Brazil., Nardelli SC; Instituto Carlos Chagas, Fundação Oswaldo Cruz, Curitiba 81350-010, Brazil. |
| Abstrakt: |
Toxoplasma gondii is an obligate intracellular parasite of the phylum Apicomplexa and causes toxoplasmosis infections, a disease that affects a quarter of the world's population and has no effective cure. Epigenetic regulation is one of the mechanisms controlling gene expression and plays an essential role in all organisms. Lysine deacetylases (KDACs) act as epigenetic regulators affecting gene silencing in many eukaryotes. Here, we focus on TgKDAC4, an enzyme unique to apicomplexan parasites, and a class IV KDAC, the least-studied class of deacetylases so far. This enzyme shares only a portion of the specific KDAC domain with other organisms. Phylogenetic analysis from the TgKDAC4 domain shows a putative prokaryotic origin. Surprisingly, TgKDAC4 is located in the apicoplast, making it the only KDAC found in this organelle to date. Transmission electron microscopy assays confirmed the presence of TgKDAC4 in the periphery of the apicoplast. We identified possible targets or/and partners of TgKDAC4 by immunoprecipitation assays followed by mass spectrometry analysis, including TgCPN60 and TgGAPDH2, both located at the apicoplast and containing acetylation sites. Understanding how the protein works could provide new insights into the metabolism of the apicoplast, an essential organelle for parasite survival. |
