Compartmentation of protein folding in vivo: sequestration of non-native polypeptide by the chaperonin-GimC system

The functional coupling of protein synthesis and chaperone-assisted folding in vivo has remained largely unexplored. Here we have analysed the chapero n-independent folding pathway of actin in yeast, Remarkably, overexpression of a heterologous chaperonin which traps non-native polypeptides does not interfere with protein folding in the cytosol, indicating a high-level orga nization of folding reactions. Newly synthesized actin avoids the chaperoni n trap and is effectively channelled from the ribosome to the endogenous ch aperonin TRiC. Efficient actin folding on TRiC is critically dependent on t he hetero-oligomeric co-chaperone GimC. By interacting with folding interme diates and with TRiC, GimC accelerates actin folding at least 5-fold and pr events the premature release of nonnative protein from TRiC, We propose tha t TRiC and GimC form an integrated 'folding compartment' which functions in cooperation with the translation machinery. This compartment sequesters ne wly synthesized actin and other aggregation-sensitive polypeptides from the crowded macromolecular environment of the cytosol, thereby allowing their efficient folding.