Buscaglia Carlos A, Campo Vanina A, Di Noia Javier M, Torrecilhas Ana C T, De Marchi Cláudia R, Ferguson Michael A J, Frasch Alberto C C, Almeida Igor C
Instituto de Investigaciones Biotecnológicas-Instituto Tecnológico de Chascomús, Universidad Nacional de General San Martín, San Martín, Buenos Aires, Argentina.
J Biol Chem. 2004 Apr 16;279(16):15860-9. doi: 10.1074/jbc.M314051200. Epub 2004 Jan 28.
A thick coat of mucin-like glycoproteins covers the surface of Trypanosoma cruzi and plays a crucial role in parasite protection and infectivity and host immunomodulation. The appealing candidate genes coding for the mucins of the mammal-dwelling stages define a heterogeneous family termed TcMUC, which comprises up to 700 members, thus precluding a genetic approach to address the protein core identity. Here, we demonstrate by multiple approaches that the TcMUC II genes code for the majority of trypomastigote mucins. These molecules display a variable, non-repetitive, highly O-glycosylated central domain, followed by a short conserved C terminus and a glycosylphosphatidylinositol anchor. A simultaneous expression of multiple TcMUC II gene products was observed. Moreover, the C terminus of TcMUC II mucins, but not their central domain, elicited strong antibody responses in patients with Chagas' disease and T. crusi infected animals. This highly diverse coat of mucins may represent a refined parasite strategy to elude the mammalian host immune system.
一层厚厚的黏蛋白样糖蛋白覆盖在克氏锥虫表面,在寄生虫保护、感染性及宿主免疫调节方面发挥着关键作用。编码哺乳动物寄生阶段黏蛋白的有吸引力的候选基因定义了一个异质家族,称为TcMUC,其成员多达700个,因此排除了通过遗传学方法确定蛋白质核心特性的可能性。在这里,我们通过多种方法证明,TcMUC II基因编码了大多数锥鞭毛体黏蛋白。这些分子具有一个可变的、非重复的、高度O-糖基化的中央结构域,其后是一个短的保守C末端和一个糖基磷脂酰肌醇锚定。观察到多个TcMUC II基因产物的同时表达。此外,TcMUC II黏蛋白的C末端而非中央结构域,在恰加斯病患者和克氏锥虫感染动物中引发了强烈的抗体反应。这种高度多样的黏蛋白外衣可能代表了寄生虫逃避哺乳动物宿主免疫系统的精妙策略。