Nagamune Kisaburo, Ohishi Kazuhito, Ashida Hisashi, Hong Yeonchul, Hino Jun, Kangawa Kenji, Inoue Norimitsu, Maeda Yusuke, Kinoshita Taroh
Department of Immunoregulation, Research Institute for Microbial Diseases, Osaka University, 3-1 Yamada-oka, Suita, Osaka 565-0871, Japan.
Proc Natl Acad Sci U S A. 2003 Sep 16;100(19):10682-7. doi: 10.1073/pnas.1833260100. Epub 2003 Sep 4.
Glycosylphosphatidylinositol (GPI) anchor is a membrane attachment mechanism for cell surface proteins widely used in eukaryotes. GPIs are added to proteins posttranslationally by a complex enzyme, GPI transamidase. Previous studies have shown that human and Saccharomyces cerevisiae GPI transamidases are similar and consist of five homologous components: GAA1, GPI8, PIG-S, PIG-T, and PIG-U in humans and Gaa1p, Gpi8p, Gpi17p, Gpi16p, and Cdc91p in S. cerevisiae. We report that GPI transamidase of Trypanosoma brucei (Tb), a causative agent of African sleeping sickness, shares only three components (TbGAA1, TbGPI8, and TbGPI16) with humans and S. cerevisiae but has two other specific components, trypanosomatid transamidase 1 (TTA1) and TTA2. GPI transamidases of both bloodstream form (growing in mammalian blood) and procyclic form (growing in tsetse fly vector) of the parasite have the same five components. Homologues of TTA1 and TTA2 are present in Leishmania and Trypanosoma cruzi but not in mammals, yeasts, flies, nematodes, plants, or malaria parasites, suggesting that these components may play unique roles in attachment of GPI anchors in trypanosomatid parasites and provide good targets for antitrypanosome drugs.
糖基磷脂酰肌醇（GPI）锚定是真核生物中广泛用于细胞表面蛋白的一种膜附着机制。GPI在翻译后由一种复合酶GPI转酰胺酶添加到蛋白质上。先前的研究表明，人和酿酒酵母的GPI转酰胺酶相似，由五个同源成分组成：人类中的GAA1、GPI8、PIG - S、PIG - T和PIG - U，以及酿酒酵母中的Gaa1p、Gpi8p、Gpi17p、Gpi16p和Cdc91p。我们报告说，非洲昏睡病病原体布氏锥虫（Tb）的GPI转酰胺酶与人和酿酒酵母仅共有三个成分（TbGAA1、TbGPI8和TbGPI16），但还有另外两个特定成分，即锥虫转酰胺酶1（TTA1）和TTA2。该寄生虫的血流形式（在哺乳动物血液中生长）和前循环形式（在采采蝇载体中生长）的GPI转酰胺酶都有相同的五个成分。TTA1和TTA2的同源物存在于利什曼原虫和克氏锥虫中，但在哺乳动物、酵母、苍蝇、线虫、植物或疟原虫中不存在，这表明这些成分可能在锥虫寄生虫的GPI锚定附着中发挥独特作用，并为抗锥虫药物提供了良好的靶点。
