Structural and Biochemical Characterisation of early Nascent Chain folding on the Ribosome (360G-Wellcome-203822_Z_16_A)

Formation of the correct tertiary structure is essential for protein function and all cellular biological processes. In vivo proteins are synthesized on the ribosome and can begin to fold co-translationally. The presence of the ribosome as well as the vectorial emergence of the nascent chain results in major differences between the folding of proteins in isolation and on the ribosome, yet there are relatively few studies on the folding of nascent chains on the ribosome. I aim to understand the early events of protein folding on the ribosome, in particular the structure and dynamics of the nascent chain as well as its interactions with the ribosome, using a hybrid of structural biology methods and biochemical techniques. Specifically, we will use NMR to gain residue specific information on nascent chain dynamics within ribosome nascent chain complexes, and cross-linking mass spectrometry to investigate nascent chain interactions. These studies will be crucial to identify any conserved mechanisms of co-translational protein folding as it occurs on the ribosome. Additionally, this study will aid in our understanding of how the ribosome is able to prevent misfolding which is linked to a broad range of devastating protein misfolding diseases.