3. Roland Beckmann - Structural basis of canonical and non-canonical translation termination and recycling by eRF1/eRF3 and ABCE1 in yeast and humans

This project addresses the essential phases of eukaryotic translation termination and ribosome recycling using the yeast (S. cerevisiae) and the human system. We aim to elucidate the molecular basis of human termination and recycling by high-resolution cryo-EM (using newly installed FEI Falcon 2 direct electron detector technology)with a focus on stop-codon recognition and peptidyl-tRNA hydrolysis by eRF1. We aim to study two variants of non-canonical termination. (1) the viral family of 2A-peptides causes a mechanism called "Stop-Go" translation, where the ribosome is stalled on a proline codon, and (2) the non-canonical stalled translation termination using the example of the fungal arginine attenuator peptide (AAP). We propose to extend our studies and use the novel direct electron detector technology to obtain cryo-EM structures at a resolution, where arginines or stalling competent arginine derivatives (RGD peptides) can unambiguously identified. This will allow for a mechanistic understanding the ribosome can act as an arginine sensor for the cell in response to another example of a non-canonical - stalled - termination event.