Study Finds Ribosomes Integral to Protein Folding Process

Researchers at University College London (UCL) have identified a critical role of ribosomes in the folding of new proteins, as detailed in their recent publication in Nature. Ribosomes, essential molecular machines for protein synthesis, not only assemble proteins but also influence their folding during synthesis, a process known as co-translational protein folding.

Understanding protein folding is vital, as misfolding can lead to numerous diseases. Traditional studies have focused on isolated polypeptides, but these new findings highlight the ribosome's significant impact on protein folding pathways, energy, and stability.

The UCL team, led by Professor John Christodoulou, used advanced imaging techniques to capture protein synthesis snapshots. They discovered that ribosomes induce expanded structures in unfolded proteins, contrasting with the more compact forms seen in bulk solutions. This "entropic destabilization" is crucial for forming co-translational folding intermediates, which are stable on the ribosome but not in isolation.

These intermediates are essential for proper protein folding and help protect nascent proteins from mutation-induced unfolding. This process is vital for protein evolution and can also contribute to disease-related misfolding events.

Professor Christodoulou emphasized the importance of these findings: “We have found that ribosomes are even more important to protein folding and misfolding processes than previously believed, suggesting that future research into this vital component of life should incorporate the role of ribosomes.”

“The majority of proteins can only fold to their active forms during their biosynthesis on the ribosome so an understanding of the process and in particular of the novel structures of the co-translational intermediates formed can be important for developing understanding disease,” Christodoulou added.