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A parasite-surface trans-sialidase of Trypanosoma cruzi

克氏锥虫寄生虫表面唾液酸转移酶

基本信息

批准号：
07670284
负责人：
UEMURA Haruki
金额：
$ 1.54万
依托单位：
Nagasaki University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1995
资助国家：
日本
起止时间：
1995 至 1996
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07670284/
关键词：
Chagas' disease Trans-sialidase sialic acid Trypanosoma Trypomastigote Gene expression GPI-anchored protein 遺伝子多様性

项目摘要

Trans-sialidase (TS) is a unique enzyme found in protozoan Trypanosoma. This enzyme catalyzes sialic acid transfer reaction from host derived glycoconjugates to parasite surface acceptor molecules. This enzyme is first found in trypomastigote stage of Trypanosoma cruzi, causative agent of Chagas' disease. The sialic acids, transferred to the parasite surface glycoprotein are suggested to be important for cell invasion and escape from host defense systems.We have analyzed the gene structure of T.cruzi trans-sialidase. Trans-sialidase is highly expressed in trypomastigote stage and the genes for these proteins are arranged in clusters of tandem array. The other type of trans-sialidase is detectable at the insect stage of parasite, epimastigote. These two types of trans-sialidase genes are localized at the different chromosomes and may be regulated independently. Catalytic domain of these two trans-sialidase molecule shear more than 80% of similarities, however these amino- and carboxyl- terminal regions have no similarities. Most remarkable differences in these enzymes are at their C-terminal. C-terminal half of trypomastigote type is tandem repeats of 12 amino acid unit and these are followed by GPI anchor structure. No these repeat and no GPI exists in epimastigote trans-sialidase. Both of the enzymes consist of several members of gene family.In these last years, We have analyzed heterogeneity of these trans-sialidase gene family. The sequence analysis of PCR amplified DNA fragments suggested that around half of the genes encode enzymatically inactive type of trans-sialidase and 30 amino acid substitutions were found in this region of 200 amino acid long. The effect of these substitutions to the enzyme activity is also examined using bacterial expression system.

转唾液酸酶（TS）是原生动物锥虫体内发现的一种独特的酶。这种酶催化唾液酸从宿主衍生的糖缀合物转移到寄生虫表面受体分子的反应。这种酶首次发现于锥虫的锥鞭毛体阶段，锥虫病的病原体克氏锥虫。研究表明，转唾液酸酶基因的结构与宿主细胞的入侵和逃逸有关。转唾液酸酶在锥鞭毛体阶段高表达，这些蛋白的基因排列成串联阵列的簇。另一种类型的转唾液酸酶在寄生虫的昆虫阶段（外鞭毛体）是可检测的。这两种类型的转唾液酸酶基因位于不同的染色体上，并且可以独立地调节。这两个转唾液酸酶分子的催化结构域剪切超过80%的相似性，但是这些氨基和羧基末端区域没有相似性。这些酶中最显著的差异在它们的C-末端。锥鞭毛体型的C-末端的一半是12个氨基酸单位的串联重复序列，并且这些串联重复序列之后是GPI锚结构。上鞭毛体转唾液酸酶不存在这些重复序列，也不存在GPI。这两种酶都由多个基因家族成员组成，近年来，我们对这两个转唾液酸酶基因家族的异质性进行了分析。PCR扩增的DNA片段的序列分析表明，大约一半的基因编码的酶失活型的转唾液酸酶和30个氨基酸的替换被发现在这200个氨基酸长的区域。还使用细菌表达系统检查这些取代对酶活性的影响。