Project Details
Projekt
Structural studies of ribosome-SelB complexes and ribosome nascent chain folding intermediates by cryo-EM and molecular dynamics simulations
Subject Area
Structural Biology
Term
from 2012 to 2020
Project identifier
Deutsche Forschungsgemeinschaft (DFG) - Project number 207100805
In P2 we will focus on the combination of high-resolution single particle cryo-EM structure determination of ribosome complexes and the subsequent detailed analysis by molecular dynamics simulations. Specifically we will address two different ribosome complexes. Our first topic is focused on selenocysteine incorporation by the elongation factor SelB and the structural dynamics of SelB interaction with the ribosome. Our second aim is to study co-translational protein folding of the model protein NemK at high resolution by time-resolved cryo-EM studies and simulations. The structure of the ribosome can now be solved by cryo-EM at resolutions that directly allow atomic model building and intermediate structures of ribosomes in different functional states during elongation factor (SelB) binding or during protein folding become accessible at this resolution level due to the latest improvements in electron microscopy hardware and image analysis. This is the starting point for detailed analysis of dynamic events by molecular dynamics simulations which provides quantitative information on energy barriers and rate constants between different functional states and finally contributes to our understanding of driving forces in ribosome function. The combination of cryo-EM and MD simulations is therefore unique to understand the molecular processes of elongation factor binding and co-translational protein folding and to obtain detailed insights into the dynamics of the ribosome at near-atomic resolution.
DFG Programme
Research Units
