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In living systems, polypeptide chains are synthesised on ribosomes, molecular machines composed of over 50 protein and nucleic acid molecules. As nascent chains emerge from the ribosomal exit tunnel and into the cellular environment, the majority must fold into specific structures in order to function. Knowledge of how this folding process occurs, and how misfolding is avoided within the cellular environment, is central to our understanding of the nature of living systems.

We have pioneered the use of NMR spectroscopy to study the co-translational folding process with near-atomic resolution, establishing strategies to prepare large quantities of isotopically enriched ribosome-nascent chain complexes. Despite the low concentration and large molecular weight of these complexes, we have shown that NMR can be a rich source of information on the structure, dynamics and folding of nascent polypeptides.

Overall, we aim to develop a detailed description of the free energy landscape of a nascent chain in the process of being translated on the ribosome, and thereby elucidate its co-translational folding, its interaction with the ribosome and the mechanism by which these interactions regulate protein translation, for which, to date, no atomic details are available.

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