Galactose Recognition by the Apicomplexan Parasite Toxoplasma gondii
Galactose Recognition by the Apicomplexan Parasite Toxoplasma gondii
复制标题
DOI：
10.1074/jbc.m111.325928
复制
发表时间：
2012-05-11
影响因子：
4.8
通讯作者：
Matthews, Stephen
中科院分区：
文献类型：
--
作者：
Marchant, Jan;Cowper, Ben;Matthews, Stephen
刚地弓形虫是顶复门的模式寄生虫，其含有许多具有医学和兽医重要性的专性细胞内寄生虫，包括艾美耳球虫属、肉孢子虫属、隐孢子虫属、环孢子虫属和疟原虫属。这个门的成员积极进入宿主细胞的一个多步骤的过程中发挥重要作用的运动，宿主细胞的附着，移动连接的形成和入侵的微线体蛋白（MIC）复合物的帮助下。T.弓形虫（Tg）MIC 1 -4-6复合物是研究最广泛的微线体复合物，其通过唾液酸结合粘附素TgMIC 1的作用而有助于宿主细胞识别和附着。在这里，我们报告的TgMIC 4的结构，并揭示其碳水化合物结合特异性的各种含半乳糖的碳水化合物配体。该凝集素由六个苹果结构域组成，其中第五个结构域显示出有效的半乳糖结合活性，并且在寄生虫入侵期间从复合物中裂解。我们提出，半乳糖识别TgMIC 4可能会损害宿主保护半乳糖凝集素介导的激活宿主免疫系统。
Toxosplasma gondii is the model parasite of the phylum Apicomplexa, which contains numerous obligate intracellular parasites of medical and veterinary importance, including Eimeria, Sarcocystis, Cryptosporidium, Cyclospora, and Plasmodium species. Members of this phylum actively enter host cells by a multistep process with the help of microneme protein (MIC) complexes that play important roles in motility, host cell attachment, moving junction formation, and invasion. T. gondii (Tg)MIC1-4-6 complex is the most extensively investigated microneme complex, which contributes to host cell recognition and attachment via the action of TgMIC1, a sialic acid-binding adhesin. Here, we report the structure of TgMIC4 and reveal its carbohydrate-binding specificity to a variety of galactose-containing carbohydrate ligands. The lectin is composed of six apple domains in which the fifth domain displays a potent galactose-binding activity, and which is cleaved from the complex during parasite invasion. We propose that galactose recognition by TgMIC4 may compromise host protection from galectin-mediated activation of the host immune system.