The EF-P paralog EfpL - Molecular characterization and physiological significance

• Applicant: Privatdozent Dr. Jürgen Lassak
• Subject Area: Metabolism, Biochemistry and Genetics of Microorganisms
• Term: since 2021
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 460364792

The translation of an mRNA sequence into an amino acid sequence is a universal process and is carried out by ribosomes. Notably, it does not always work smoothly. In Escherichia coli, for example, the ribosome gets stuck in every 25th case. One of the most common causes of this are polyproline sequences. Therefore, in almost all organisms there is a specialized elongation factor, called EF-P in bacteria, which facilitates the translation of these difficult sequences. In about 7% of all bacteria, a paralogous protein YeiP (EfpL) with hitherto unknown function is present besides the canonical EF-P. In first experiments we were able to show that this protein is able to partially compensate the cellular defects caused by the loss of EF-P in the Gram-negative model organism Escherichia coli and thus appears to have an accessory and specialized function in resolving the polyproline-induced ribosome arrest. In the framework of the proposal we want to quantitatively describe the arrest motif spectrum of EfpL by systematic and global analyses and characterize the enzyme biochemically and structurally. This also includes the synthetic functionalization of EfpL by the EF-P specific modification systems EpmA and EarP. This will not only provide us with insights into their acceptor substrate specificity, but also with new ideas about the molecular mode of action at the ribosome. In addition, the data obtained will also allow us to draw conclusions about the evolution of different EF-P subtypes.

• DFG Programme: Research Grants