Abstract

The Posttranslational Concept of Protein Folding: How Valid Is It?

M. A. Basharov

Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences, Pushchino, Moscow Region, 142290 Russia; fax: (7-0967) 79-0553; E-mail: basharov@venus.iteb.serpukhov.su

Received December 10, 1999; Revision received May 29, 2000
Two concepts of protein folding are known. One of them, the cotranslational concept, states that a protein folds during the synthesis of the polypeptide chain on the ribosome. According to the other, the posttranslational concept, the protein starts to fold just after the synthesis of its polypeptide chain. This article attempts to show that the posttranslational concept is hardly suited to solve the problem of protein folding. In our opinion, polypeptide chains cannot be represented as random coils. They are stiff chain-like macromolecules rather than flexible ones: the single bond rotational barriers of a polypeptide substantially exceed the accepted standard values; even in strong denaturing conditions, a protein possesses a considerable amount of residual folded structures. We believe that the popular “hierarchical” models for the protein folding mechanism are not realistic because the formation of secondary and tertiary structures of proteins occurs simultaneously and cooperatively. The time for the elongation of a polypeptide chain by one amino acid residue during biosynthesis exceeds considerably the time of the formation of alpha-helices and beta-sheets in proteins as well as the time supposed for the spatial structure formation of a native protein during renaturation. Thus, we believe that the mechanism of protein folding in vivo cannot be clarified by denaturation-renaturation experiments. In our opinion, the phenomenon of protein renaturation is no more than the restoration of native protein conformation (which initially forms cotranslationally) disrupted during denaturation, and thus denaturation-renaturation experiments cannot serve as a model to clarify the mechanism of protein folding.
KEY WORDS: protein folding, mechanism of folding, posttranslational folding, folding models, random coil, barriers in proteins, protein renaturation, protein elasticity