WHY STUDY CHAPERONE-MEDIATED PROTEIN FOLDING?

Understanding how proteins fold in the cell is a central problem in modern biology. The transformation of the one-dimensional genetic information into three-dimensional protein structures depends on the accuracy and efficiency of the process of protein folding and the maintenance of this correct conformation is essential for protein function and hence for the life of the cell. While in vitro folding experiments have shown that the process can occur spontaneously, it appears that several protein families, generically termed molecular chaperones, are required for the correct folding and assembly of proteins in the cell. Despite considerable progress in the biochemical and biophysical analysis of molecular chaperones, surprisingly little is known about how protein folding occurs in vivo, following translation by cytosolic ribosomes. Progress in this area has been hindered by the lack of experimental approaches to study the folding intermediates of newly translated proteins in the complex cellular environment found in both translation lysates and intact cells. Our research aim is to examine the chaperone-interactions and folding intermediates of newly translated polypeptides under physiological conditions. By emphasizing folding events as they occur at the ribosome during synthesis of a polypeptide we will be able to understand the pathways of protein folding in eukaryotic cells and how this folding is regulated.