Folding of newly translated proteins in vivo: The role of molecular chaperones

Recent years have witnessed dramatic advances in our understanding of how n ewly translated proteins fold in the cell and the contribution of molecular chaperones to this process. Folding in the cell must be achieved in a high ly crowded macromolecular environment, in which release of nonnative polype ptides into the cytosolic solution might lead to formation of potentially t oxic aggregates. Here I review the cellular mechanisms that ensure efficien t folding of newly translated proteins in vivo. De novo protein folding app ears to occur in a protected environment created by a highly processive cha perone machinery that is directly coupled to translation. Genetic and bioch emical analysis shows that several distinct chaperone systems, including Hs p70 and the cylindrical chaperonins, assist the folding of proteins upon tr anslation in the cytosol of both prokaryotic and eukaryotic cells. The cell ular chaperone machinery is specifically recruited to bind to ribosomes and protects nascent chains and folding intermediates from nonproductive inter actions. In addition, initiation of folding during translation appears to b e important for efficient folding of multidomain proteins.