Modification of elongation factor eEF1A by Legionella pneumophila Lgt glucosyltransferases

嗜肺军团菌是一种称为军团菌病的严重肺炎的病因。病原体在宿主细胞中的军团菌复制空泡中发育，并产生许多效应蛋白，这些效应蛋白被转移到宿主细胞胞质溶胶中。先前我们鉴定了军团菌葡糖基转移酶Lgt 1、2和3，其在丝氨酸-53处葡糖基化真核延伸因子1A（eEF 1A），从而抑制宿主的蛋白质合成。本研究的目的是阐明潜在的Lgt诱导的蛋白质合成抑制的分子机制。蛋白质组学分析应澄清Lgt对参与感染的单个蛋白质翻译的影响。由于先前的工作表明eEF 1A的丝氨酸-53磷酸化，因此应分析磷酸化的作用并与Lgt诱导的葡萄糖基化进行比较。Lgts在分子结构上有很大的不同，因此我们的目的是分析Lgts的结构-功能关系。这些研究应该深入了解军团菌效应子抑制蛋白质合成的作用，并应该促进我们对它们在军团菌感染中的作用的理解。此外，我们的研究结果应该允许新的见解内源性调节蛋白质合成。

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.