Oury Bruno, Tarrieu Frédérique, Monte-Alegre Adriano, Ouaissi Ali
Institut de Recherche pour le Développement (IRD), Unité de Recherche no 8 Pathogénie des Trypanosomatidae, Montpellier, France.
Exp Parasitol. 2005 Nov;111(3):198-206. doi: 10.1016/j.exppara.2005.07.001. Epub 2005 Sep 30.
We have previously identified a Trypanosoma cruzi gene encoding a protein named Tc52 sharing structural and functional properties with the thioredoxin and glutaredoxin family involved in thiol-disulfide redox reactions. Gene targeting strategy and immunological studies allowed showing that Tc52 is among T. cruzi virulence factors. Taking into account that T. cruzi has a genetic variability that might be important determinant that governs the different behaviour of T. cruzi clones in vitro and in vivo, we thought it was of interest to analyse the sequence polymorphism of Tc52 gene in several reference clones. The DNA sequences of 12 clones which represent the whole genetic diversity of T. cruzi allowed showing that 40 amino-acid positions over 400 analysed are targets for mutations. A number of residues corresponding to putative amino-acids playing a role in GSH binding and/or enzymatic function and others located nearby are subject to mutations. Although the immunological analysis showed that Tc52 is present in parasite extracts from different clones, it is possible that the amino-acid differences could affect the enzymatic and/or the immunomodulatory function of Tc52 variants and therefore the parasite phenotype.
我们之前鉴定出一种克氏锥虫基因,其编码一种名为Tc52的蛋白质,该蛋白质与参与硫醇 - 二硫键氧化还原反应的硫氧还蛋白和谷氧还蛋白家族具有结构和功能特性。基因靶向策略和免疫学研究表明Tc52是克氏锥虫的毒力因子之一。考虑到克氏锥虫具有遗传变异性,这可能是决定其不同克隆在体外和体内表现不同行为的重要因素,我们认为分析几个参考克隆中Tc52基因的序列多态性很有意义。代表克氏锥虫全部遗传多样性的12个克隆的DNA序列显示,在分析的400个氨基酸位置中有40个位置是突变靶点。一些与推测在谷胱甘肽结合和/或酶功能中起作用的氨基酸相对应的残基以及附近的其他残基都发生了突变。尽管免疫学分析表明Tc52存在于不同克隆的寄生虫提取物中,但氨基酸差异可能会影响Tc52变体的酶促和/或免疫调节功能,进而影响寄生虫表型。