Folding of a nascent peptide on the ribosome.

Even though very significant progress has been made recently in elucidating the structure of the bacterial ribosome and topological assignments of its functional parts, the molecular mechanism of how a peptide is formed and how the nascent peptides is folded on the ribosomes remains uncertain. Here, the current progress and remaining problems are considered from the standpoint of the authors. Topics considered include formation of peptide bonds and models that represent this process, the vicinity of RNA to the nascent peptide, the cotranslational folding hypothesis, evidence that some but not all nascent peptides pass through a region within the 50S ribosomal subunit, presumably the tunnel, in which they are folded and sheltered, pause-site peptides, and the involvement of chaperones in folding of nascent proteins on ribosomes. The chaperone-like activity of the large ribosomal subunit in renaturation of denatured proteins is reviewed. It is concluded that cotranslational folding of some but not all nascent peptides occurs in the large ribosomal subunit. It is suggested that this folding is facilitated by changes in the conformation of the ribosome that are related to the reaction cycle of peptide elongation.