Biosynthetic Protein Folding and Molecular Chaperons

Abstract

The problem of linear polypeptide chain folding into a unique tertiary structure is one of the fundamental scientific challenges. The process of folding cannot be fully understood without its biological context, especially for big multidomain and multisubunit proteins. The principal features of biosynthetic folding are co-translational folding of growing nascent polypeptide chains and involvement of molecular chaperones in the process. The review summarizes available data on the early events of nascent chain folding, as well as on later advanced steps, including formation of elements of native structure. The relationship between the non-uniformity of translation rate and folding of the growing polypeptide is discussed. The results of studies on the effect of biosynthetic folding features on the parameters of folding as a physical process, its kinetics and mechanisms, are presented. Current understanding and hypotheses on the relationship of biosynthetic folding with the fundamental physical parameters and current views on polypeptide folding in the context of energy landscapes are discussed.

Keywords: chaperones; co-translational folding; protein biosynthesis; protein folding.