PROTEIN-FOLDING IN THE CYTOSOL - CHAPERONIN-DEPENDENT AND CHAPERONIN-INDEPENDENT MECHANISMS

Recent findings suggest that a combination of chaperonin-assisted and unassisted mechanisms operate in protein folding in the cytosol, While nascent chain-binding chaperones, such as Hsp70, could have a general role in maintaining the folding competence of translating polypeptide chains, the contribution of the cylindrical chaperonin complexes to o verall folding is limited to a subset of aggregation-sensitive polypep tides. The majority of bacterial proteins are relatively small and the y are synthesized rapidly and folded independently of the chaperonin G roEL in a posttranslational manner, Eukaryotes have a proportionally l arger number of multi-domain proteins than bacteria, The individual do mains of these proteins can be folded co-translationally and sequentia lly, The use of this mechanism explains how large proteins fold indepe ndently of a chaperonin and could have been crucial in the evolution o f a wide array of modular polypeptides in eukaryotes,