1. Christian Spahn - Translational GTPases and the energy landscape of the 70S ribosome

Translational GTPases (trGTPases) constitute an important group of external translation factors. They control and steer the ribosome during all four phases of protein synthesis. trGTPases usually bind to a specific state of the ribosome in their GTP conformation and dissociate in their GDP conformation. Consequently, there are complex dynamic molecular interactions and interdependences during the functional cycle within the various intermediates. GTP hydrolysis and phosphate release may be critical steps in defining the molecular interplay with the ribosome. In the metastable energy landscape view the ribosome can be regarded as a Brownian machine capable of sampling several conformational states at ambient temperature. trGTPases can tune the energy landscape resulting in apparent large-scale conformational changes in the ribosome or the factor by a conformational capture mechanism. Here we want to structurally analyze the complex interplay between canonical translational GTPase factors with the bacterial 70S ribosome using multiparticle cryo-EM. This will allow us to solve the structure and conformational modes of various complexes of the 70S ribosomes with a trGTPase stalled on the ribosome in a variety of experimental conditions, e.g. using antibiotics or non-hydrolysable GTP analogues.