Fragoso Mariana Sayuri Ishikawa, de Siqueira Caroline Moraes, Vitorino Francisca Nathália Luna, Vieira Alexandre Zanatta, Martins-Duarte Érica Santos, Faoro Helisson, da Cunha Júlia Pinheiro Chagas, Ávila Andréa Rodrigues, Nardelli Sheila Cristina
Instituto Carlos Chagas, Fundação Oswaldo Cruz, Curitiba 81350-010, Brazil.
Special Laboratory of Cell Cycle, Center of Toxins, Immune Response and Cell Signalling (CeTICS), Instituto Butantan, São Paulo 05503-900, Brazil.
Microorganisms. 2023 Jun 12;11(6):1558. doi: 10.3390/microorganisms11061558.
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.
是顶复门的专性细胞内寄生虫,可引起弓形虫感染,这种疾病影响着全球四分之一的人口,且尚无有效治愈方法。表观遗传调控是控制基因表达的机制之一,在所有生物体中都起着至关重要的作用。赖氨酸脱乙酰酶(KDACs)作为表观遗传调节因子,在许多真核生物中影响基因沉默。在这里,我们聚焦于TgKDAC4,这是一种顶复门寄生虫特有的酶,属于IV类KDAC,是迄今为止研究最少的一类脱乙酰酶。这种酶与其他生物体仅共享部分特定的KDAC结构域。对TgKDAC4结构域的系统发育分析显示其可能起源于原核生物。令人惊讶的是,TgKDAC4位于质体中,使其成为迄今为止在该细胞器中发现的唯一一种KDAC。透射电子显微镜分析证实了TgKDAC4存在于质体周边。我们通过免疫沉淀分析结合质谱分析确定了TgKDAC4可能的靶点或/和伙伴,包括TgCPN60和TgGAPDH2,它们都位于质体中且含有乙酰化位点。了解这种蛋白质的工作方式可能为质体的代谢提供新的见解,质体是寄生虫生存所必需的细胞器。