Heat shock proteins in protein folding and membrane translocation

Constitutively expressed heat-shock proteins of the hsp60 and hsp70 families, classified as 'molecular chaperones', have important functions in the folding and intracellular sorting of newly-synthesized proteins. Recent studies of protein translocation across subcellular membranes have shown: (1) Proteins traverse membranes in extended conformations. (2) Cytosolic hsp70 proteins maintain newly-synthesized precursors destined for translocation in a loosely-folded, translocation-competent state. (3) Hsp 70 proteins on the trans-side of the membrane are required for efficient translocation. (4) In the case of mitochondria, the newly-imported polypeptides are transferred to the 'foldase' hsp60, the homologue of the E. coli groEL, which mediates their folding and oligomeric assembly. Hsp70 and hsp60 fulfill these various functions by their abilities, (1) to recognize an unknown structural element(s) which is transiently exposed in unfolded or incompletely folded polypeptides, and (2) to allow cycles of binding and (step-wise) release of the substrate protein catalyzed by ATP-hydrolysis.