Modification of elongation factor eEF1A by Legionella pneumophila Lgt glucosyltransferases

• Applicant: Professor Dr. Klaus Aktories
• Subject Area: Parasitology and Biology of Tropical Infectious Disease Pathogens ; Pharmacology
• Term: from 2014 to 2018
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 253214820

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.

• DFG Programme: Research Grants
• Participating Person: Dr. Thomas Jank