Molecular Chaperones HSP70 and HSP60 in Protein Folding and Membrane Translocation

Abstract

Given the difficulties protein chemists may encounter when attempting to renature unfolded proteins in vitro,it is noteworthy that the acquisition of the correctly folded structure seems to be much less of a traumatic experience for a nascent polypeptide chain in vivo. Generally, unfolded polypeptides have the tendency to aggregate. The cellular environment with its extremely high concentration of total protein (~0.3 g/ml) and of newly-synthesized, folding chains (30–50 μM in Escherichia coli) may result in even further reduction of solubility and thus should strongly favor misfolding and aggregation of a folding protein (Zimmerman and Trach, 1991). Nevertheless, the yield of folded protein in vivo can reach almost 100% (Gething et al., 1986). It has become clear over recent years that the action of molecular chaperones, helper proteins which interact with folding intermediates and prevent unproductive off-pathway reactions (Ellis, 1987; Rothman, 1989; Gething and Sambrook, 1992), is essential in accomplishing this high efficiency of physiological protein folding.