Research highlights 2004-2008

After determining the first solution structures of the inactive and active 80S ribosome-Sec61 complex we focussed on the complexes involved in targeting. We could solve the structure of a eukaryotic targeting complex consisting of an active ribosome (RNC) and SRP. Here, we learned how SRP binds to the signal sequence of a nascent polypeptide and modulates the activity of the ribosome at the same time. Later, we observed a bacterial and also the eukaryotic targeting complex at sub-nanometer resolution allowing the visualization of the signal sequence bound to SRP. We could also show that the signal sequence is positioned on the ribosome in a distinct way for recognition by SRP. Next, a docking complex binding the SRP receptor was solved, that revealed how the first membrane contact of the targeted ribosome may occur. Most recently, we succeeded to observe the active monomeric ribosome-bound Sec61 complex as well as the bacterial ribosome-SecYEG complex in its membrane environment also at sub-nanometer resolution. We could explain the mode of binding to the ribosome and the interaction of the protein-conducting channel with the nascent chain. With ever improving resolution we are now able to visualize nascent chains in the ribosomal tunnel and study their behavior.