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C-Mannosylation of Toxoplasma gondii proteins promotes attachment to host cells and parasite virulence.
Journal of Biological Chemistry ( IF 4.0 ) Pub Date : 2019-12-20 , DOI: 10.1074/jbc.ra119.010590
Andreia Albuquerque-Wendt 1 , Damien Jacot 2 , Nicolas Dos Santos Pacheco 2 , Carla Seegers 1 , Patricia Zarnovican 1 , Falk F R Buettner 1 , Hans Bakker 1 , Dominique Soldati-Favre 2 , Françoise H Routier 3
Affiliation  

C-Mannosylation is a common modification of thrombospondin type 1 repeats present in metazoans and recently identified also in apicomplexan parasites. This glycosylation is mediated by enzymes of the DPY19 family that transfer α-mannoses to tryptophan residues in the sequence WX 2WX 2C, which is part of the structurally essential tryptophan ladder. Here, deletion of the dpy19 gene in the parasite Toxoplasma gondii abolished C-mannosyltransferase activity and reduced levels of the micronemal protein MIC2. The loss of C-mannosyltransferase activity was associated with weakened parasite adhesion to host cells and with reduced parasite motility, host cell invasion, and parasite egress. Interestingly, the C-mannosyltransferase-deficient Δdpy19 parasites were strongly attenuated in virulence and induced protective immunity in mice. This parasite attenuation could not simply be explained by the decreased MIC2 level and strongly suggests that absence of C-mannosyltransferase activity leads to an insufficient level of additional proteins. In summary, our results indicate that T. gondii C-mannosyltransferase DPY19 is not essential for parasite survival, but is important for adhesion, motility, and virulence.

中文翻译:

弓形虫蛋白的C-甘露糖基化促进与宿主细胞的附着和寄生虫毒力。

C-甘露糖基化是在后生动物中存在的血小板反应蛋白1型重复序列的常见修饰,最近在apicomplexan寄生虫中也被发现。这种糖基化作用是由DPY19家族的酶介导的,该酶将α-甘露糖转移到序列WX 2WX 2C的色氨酸残基上,该序列是结构上必不可少的色氨酸阶梯的一部分。在这里,dpy19基因​​在弓形虫的寄生虫中的删除消除了C-甘露糖基转移酶的活性,并降低了微Nemalmal蛋白MIC2的水平。C-甘露糖基转移酶活性的丧失与寄生虫对宿主细胞的粘附减弱以及寄生虫运动性降低,宿主细胞入侵和寄生虫外出有关。有趣的是,C-甘露糖基转移酶缺陷型Δdpy19寄生虫的毒性大大减弱,并诱导了小鼠的保护性免疫。这种寄生虫的衰减不能简单地通过MIC2水平的降低来解释,并强烈表明C-甘露糖基转移酶活性的缺乏会导致其他蛋白质的水平不足。总而言之,我们的结果表明,弓形虫C-甘露糖基转移酶DPY19对寄生虫的生存不是必需的,但对粘附,运动和毒力却很重要。
更新日期:2020-01-24
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