Apicomplexan C-Mannosyltransferases Modify Thrombospondin Type I-containing Adhesins of the TRAP Family
Apicomplexan C-Mannosyltransferases Modify Thrombospondin Type I-containing Adhesins of the TRAP Family
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DOI：
10.1093/glycob/cwy013
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发表时间：
2018-05-01
期刊：
影响因子：
4.3
通讯作者：
Routier, Francoise H.
中科院分区：
文献类型：
--
作者：
Hoppe, Carolin M.;Albuquerque-Wendt, Andreia;Routier, Francoise H.
在许多后生动物物种中，一种不寻常的蛋白质糖基化类型，称为 C-甘露糖基化，发生在粘附性血小板反应蛋白 1 型重复序列 (TSR) 和 I 型细胞因子受体上。这种修饰已被证明是由秀丽隐杆线虫 DPY-19 蛋白催化的，并且在顶复门寄生虫的基因组中发现了编码基因的直系同源物。最近，微线粘附素血小板反应蛋白相关匿名蛋白 (TRAP) 在恶性疟原虫子孢子中被证明是 C-己糖基化的。在这里，我们证明弓形虫弓形虫分泌的微线蛋白 MIC2 也是 C-己糖基化的。当在 C-甘露糖基化缺陷的哺乳动物细胞系中表达时，恶性疟原虫和刚地弓形虫 Dpy19 同源物能够修饰参与寄生虫运动和入侵的微线粘附素 TRAP/MIC2 家族的 TSR 结构域。在体外，apicomplexan 酶可以将甘露糖转移到 WXXWXXC 肽，但与秀丽隐杆线虫或哺乳动物 C-甘露糖基转移酶相反，它们对短 WXXW 肽无活性。由于 TSR 结构域常见于 apicomplexan 表面蛋白中，因此 C-甘露糖基化可能是该门中的常见修饰。
In many metazoan species, an unusual type of protein glycosylation, called C-mannosylation, occurs on adhesive thrombospondin type 1 repeats (TSRs) and type I cytokine receptors. This modification has been shown to be catalyzed by the Caenorhabditis elegans DPY-19 protein and orthologues of the encoding gene were found in the genome of apicomplexan parasites. Lately, the micronemal adhesin thrombospondin-related anonymous protein (TRAP) was shown to be C-hexosylated in Plasmodium falciparum sporozoites. Here, we demonstrate that also the micronemal protein MIC2 secreted by Toxoplasma gondiitachyzoites is C-hexosylated. When expressed in a mammalian cell line deficient in C-mannosylation, P. falciparum and T. gondii Dpy19 homologs were able to modify TSR domains of the micronemal adhesins TRAP/MIC2 family involved in parasite motility and invasion. In vitro, the apicomplexan enzymes can transfer mannose to a WXXWXXC peptide but, in contrast to C. elegans or mammalian C-mannosyltransferases, are inactive on a short WXXW peptide. Since TSR domains are commonly found in apicomplexan surface proteins, C-mannosylation may be a common modification in this phylum.