Roles of molecular chaperones in cytoplasmic protein folding

Newly synthesized polypeptide chains must fold and assemble into unique thr ee-dimensional structures in order to become functionally active. In many c ases productive folding depends on assistance from molecular chaperones, wh ich act in preventing off-pathway reactions during folding that lead to agg regation. The inherent tendency of incompletely folded polypeptide chains t o aggregate is thought to be strongly enhanced in vivo by the high macromol ecular concentration of the cellular solution, resulting, in crowding effec ts, and by the close proximity of nascent polypeptide chains during synthes is on polyribosomes. The major classes of chaperones acting in cytoplasmic protein folding are the Hsp70s and the chaperonins. Hsp70 chaperones shield the hydrophobic regions of nascent and incompletely folded chains, whereas the chaperonins provide a sequestered environment in which folding can pro ceed unimipaired by intermolecular interactions between non-native polypept ides. These two principles of chaperone action can function in a coordinate d manner to ensure the efficiency nt folding of a subset of cytoplasmic pro teins.