Effector glycosyltransferases of the human pathogen Legionella pneumophila

人类病原体嗜肺军团菌的效应糖基转移酶

• 批准号: 233993717
• 负责人: Professor Dr. Klaus Aktories
• 金额: --
• 依托单位: Abteilung I
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2013
• 资助国家: 德国
• 起止时间: 2012-12-31 至 2016-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/233993717?language=en
• 关键词: Effector; glycosyltransferases; human; pathogen; Legionella

Legionella pneumophila is a human pathogen, which causes severe pneumonia called Legionnaires disease. The bacterium invades and replicates inside alveolar macrophages. Therefore, Legionella injects effector proteins by type-IV-secretion into the host cytosol to arrange an intracellular Legionella-containing vacuole (LCV) where Legionella can replicate. The Legionella effectors SetA and Lpg1961 show high sequence similarities to glycosyltransferases and are toxic when introduced into eukaryotic cells. SetA was implicated in the subversion of eukaryotic vesicle trafficking. The function of Lpg1961 is unknown. Initial biochemical studies showed that SetA possesses an N-terminal glycosyltransferase domain and a C-terminal PtdIns(3)P-binding domain. Using yeast genetics, cell biology and protein biochemical methods, the host substrates of the glycosyltransferases should be identified and the molecular and functional consequences of their glycosylation elucidated. We aim to analyze the structure-function relationships of glycosyltransferases SetA and Lpg1961. The proposed studies should clarify the effects of the glycosyltransferases in the host cells and their roles during the Legionella infection process.

嗜肺军团菌是一种人类病原体，可引起严重的肺炎，称为军团菌病。细菌侵入并在肺泡巨噬细胞内复制。因此，军团菌通过IV型分泌将效应蛋白注入宿主细胞质中，以排列细胞内含有军团菌的空泡（LCV），军团菌可以在其中复制。军团菌效应子SetA和Lpg1961显示出与糖基转移酶的高度序列相似性，并且当引入真核细胞中时是有毒的。SetA参与真核生物囊泡运输的颠覆。Lpg 1961的功能尚不清楚。初步的生物化学研究表明SetA具有N端糖基转移酶结构域和C端PtdIns（3）P结合结构域。利用酵母遗传学、细胞生物学和蛋白质生物化学方法，应鉴定糖基转移酶的宿主底物，并阐明其糖基化的分子和功能后果。我们的目的是分析糖基转移酶SetA和Lpg 1961的结构与功能的关系。建议的研究应阐明宿主细胞中的糖基转移酶的作用及其在军团菌感染过程中的作用。