Structural characterization of an anti trans-translation peptide

In this project, the structure of the stalled ribosome with a 26-amino acid peptide known to interfere with trans-translation, will be determined to near-atomic resolution using Single Particle Analysis and cryo-EM. This technique has become a method of choice for studying the 3D structure of large macromolecular complexes, in a fully hydrated state, so conformational changes directly linked to their biological activities can studied. Since trans–translation is important for pathogen virulence and does not exist in eukaryotic cells, it represents a very attractive target for the development of new narrow-spectrum antibiotics. The proposed project aims at studying the molecular interactions between peptide mimicking the C-terminal tail of SmpB and stalled E. coli ribosomes by using advances structural approaches, in order to develop/optimize new trans-translation inhibitors.