GROWING-UP IN A DANGEROUS ENVIRONMENT - A NETWORK OF MULTIPLE TARGETING AND FOLDING PATHWAYS FOR NASCENT POLYPEPTIDES IN THE CYTOSOL

The first events in the lives of proteins are the most hazardous. Star ting at the ribosome, nascent polypeptides undergo complex folding pro cesses endangered by aggregation reactions. Proteins with organellar d estinations require correct targeting to the translocation machineries and prevention from premature folding. The high precision and speed o f these processes is ensured by a cytosolic system consisting of molec ular chaperones, folding catalysts and targeting factors. This review focuses on the interactions of this system with nascent polypeptides a nd discusses new concepts for protein folding in the cytosol. It is pr oposed that folding and targeting are promoted by a flexible network o f multiple unassisted and assisted pathways.