HOW DO PROTEINS FOLD

Understanding the mechanism by which an unfolded polypeptide chain fol ds to its unique, functional structure is a primary unsolved problem i n biochemistry. Fundamental advances towards understanding how protein s fold have come from kinetic studies, Kinetic studies allow the disse ction of the folding pathway of a protein into individual steps that a re defined by partially-structured folding intermediates. Improvements in both the structural and temporal resolution of physical methods th at are used to monitor the folding process, as well as the development of new methodologies, are now making it possible to obtain detailed s tructural information on protein folding pathways. The protein enginee ring methodology has been particularly useful in characterizing the st ructures of folding intermediates as well as the transition state of f olding, Several characteristics of protein folding pathways have begun to emerge as general features for the folding of many different prote ins. Progress in our understanding of how structure develops during fo lding is reviewed here.