Modification of elongation factor eEF1A by Legionella pneumophila Lgt glucosyltransferases

嗜肺军团菌 Lgt 葡萄糖基转移酶对延伸因子 eEF1A 的修饰

• 批准号: 253214820
• 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: 2014
• 资助国家: 德国
• 起止时间: 2013-12-31 至 2017-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/253214820?language=en
• 关键词: Modification; elongation; factor; eEF1A; Legionella

The species Legionella pneumophila is the cause of a severe pneumonia called Legionnaires disease. The pathogens develop in a Legionella replicative vacuole in host cells and produce numerous effector proteins, which are translocated into the host cell cytosol. Previously we identified the Legionella glucosyltransferases Lgt1, 2 and 3, which glucosylate eukaryotic elongation factor 1A (eEF1A) at serine-53 thereby inhibiting protein synthesis of the host. Aim of the present studies is elucidation of the molecular mechanisms underlying Lgt-induced inhibition of protein synthesis. Proteome analyses should clarify Lgt-effects on translation of individual proteins involved in infection. Because previous work showed phosphorylation of serine-53 of eEF1A, role of phosphorylation should be analyzed and compared with Lgt-induced glucosylation. Lgts are largely different in their molecular architecture, we therefore aim to analyze the structure-function relationships of Lgts. The studies should gain insights into the actions of Legionella effectors that inhibit protein synthesis, and should advance our understanding of their role in Legionella infection. Moreover, our results should allow new insights into endogenous regulation of protein synthesis.

嗜肺军团菌是一种叫做军团病的严重肺炎的病因。病原菌在宿主细胞的军团菌复制液泡中发育，产生大量效应蛋白，这些效应蛋白转运到宿主细胞的细胞质中。之前我们发现了军团菌葡萄糖基转移酶Lgt1, 2和3，它们在丝氨酸-53上葡萄糖化真核延伸因子1A (eEF1A)，从而抑制宿主的蛋白质合成。本研究的目的是阐明lgt诱导的蛋白质合成抑制的分子机制。蛋白质组学分析应阐明lgt对感染中涉及的单个蛋白质翻译的影响。由于先前的研究显示eEF1A的丝氨酸-53有磷酸化，因此应该分析磷酸化的作用，并将其与lgt诱导的糖基化进行比较。lgt在分子结构上有很大的不同，因此我们旨在分析lgt的结构-功能关系。这些研究应该深入了解军团菌效应物抑制蛋白质合成的作用，并应该促进我们对其在军团菌感染中的作用的理解。此外，我们的结果应该为蛋白质合成的内源性调节提供新的见解。

项目成果

Protein glutaminylation is a yeast-specific posttranslational modification of elongation factor 1A

• DOI: 10.1074/jbc.m117.801035
• 发表时间: 2017-09-29
• 期刊: JOURNAL OF BIOLOGICAL CHEMISTRY
• 影响因子: 4.8
• 作者: Jank, Thomas;Belyi, Yury;Aktories, Klaus
• 通讯作者: Aktories, Klaus

The Legionella effector LtpM is a new type of phosphoinositide-activated glucosyltransferase

• DOI: 10.1074/jbc.ra118.005952
• 发表时间: 2019-02-22
• 期刊: JOURNAL OF BIOLOGICAL CHEMISTRY
• 影响因子: 4.8
• 作者: Levanova, Nadezhda;Mattheis, Corinna;Schroeder, Gunnar Neels
• 通讯作者: Schroeder, Gunnar Neels

Purification and Analysis of Effector Glucosyltransferase Lgt1 from Legionella pneumophila.

嗜肺军团菌效应葡萄糖基转移酶 Lgt1 的纯化和分析

• DOI: 10.1007/978-1-4939-9048-1_18
• 发表时间: 1921
• 期刊: Methods in molecular biology
• 作者: Levanova N;Tabakova I;Jank T;Belyi Y
• 通讯作者: Belyi Y