ABSTRACT

Events involved in the earliest stages of protein synthesis and maturation only now are beginning to be understood. While considerable progress has been realized in the identification and characterization of the different machineries involved in protein synthesis (e.g. large and small ribosomal subunits, initiation, elongation and release factors), relatively little is known about the nature of a polypeptide while it is being synthesized on the ribosome. Whether folding of a nascent polypeptide occurs cotranslationally or post-translationally (or both), and whether other factors are involved in the folding process are questions that now are beginning to be addressed by different laboratories. Here, we review our current understanding of nascent chain biogenesis in the cytoplasm of both prokaryotes and eukaryotes. We begin by discussing some of the potential problems a nascent polypeptide might encounter during the different stages of its maturation. Next a description of cytosolic components which appear dedicated to interacting with nascent polypeptides destined for transport across cellular membranes will be presented. Finally, we review our current understanding of the maturation pathway of cytoplasmic proteins. Here particular attention will be paid to the description of cellular components which interact with nascent polypeptides and how these components influence the folding pathway.