Measuring cotranslational folding of nascent polypeptide chains on ribosomes

Protein folding has been studied extensively in vitro, but much less is known about how folding proceeds in vivo. A particular distinction of folding in vivo is that folding begins while the nascent polypeptide chain is still undergoing synthesis by the ribosome. Studies of cotranslational protein folding are inherently much more complex than classical in vitro protein folding studies, and historically there have been few methods available to produce the quantities of pure material required for biophysical studies of the nascent chain, or assays to specifically interrogate its conformation. However, the past few years have produced dramatic methodological advances, which now place cotranslational folding studies within reach of more biochemists, enabling a detailed comparison of the earliest stages of protein folding on the ribosome to the wealth of information available for the refolding of full-length polypeptide chains in vitro.