The effect of molecular chaperones on in vivo and in vitro folding processes.

Numerous successful experiments of in vitro protein folding demonstrate that all information required for the formation of the native, three-dimensional structure of a protein is encoded in the amino acid sequence. Thus, in vivo folding was long considered an autonomous process unaffected by other proteins or cellular components. This central paradigm of in vivo protein structure formation was abandoned with the identification of molecular chaperones which facilitate protein folding both in vitro and in vivo. Recently, mechanistic details of chaperone action have been analyzed at a molecular level. Members of the molecular chaperone families seem to fulfil different tasks along the folding pathway. Understanding the mechanism of the chaperone machinery will help to design efficient folding processes for the in vitro folding of misfolded recombinant proteins. Furthermore, cellular fine-tuning of the chaperone machinery may provide new tools for the prevention of misfolding of recombinant proteins.