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10 Molecular Chaperone Functions of hsp70 and hsp60 in Protein Folding

Judith Frydman, Franz-Ulrich Hartl


Molecular chaperones have the general property of interacting with other proteins in their nonnative conformations. The chaperones of the hsp70 and hsp60 families function by preventing aggregation of newly synthesized polypeptides, and they then mediate their folding to the native state in an ATP-dependent process. Both classes of components are functionally distinct but can cooperate in a sequential folding pathway that has been reconstituted in vitro. Intensive functional studies of these proteins have led to a revision of the long-held view that protein folding in the cell is a spontaneous process. In this chapter, we discuss the mechanistic principles of hsp70 and hsp60 action in protein folding.

All of the information necessary for a polypeptide chain to fold to its native state is contained within its amino acid sequence (Anfinsen 1973). How the information present in the linear sequence of amino acid building blocks is transformed into a unique three-dimensional structure is not yet clear. However, considerable progress has been made by biophysicists in understanding the pathways through which a defined, thermodynamically stable structure arises from the astronomically large number of conformations the polypeptide chain adopts in the unfolded state (Jaenicke 1987). Many examples exist, especially for small proteins, where folding occurs spontaneously in vitro after the unfolded polypeptide is diluted from denaturant into aqueous solution. The pathway followed by globular proteins involves the restriction of conformational space by the very rapid collapse (within milliseconds) of hydrophobic residues to the...

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