Protein folding: a perspective for biology, medicine and biotechnology

Abstract

At the present time, protein folding is an extremely active field of research including aspects of biology, chemistry, biochemistry, computer science and physics. The fundamental principles have practical applications in the exploitation of the advances in genome research, in the understanding of different pathologies and in the design of novel proteins with special functions. Although the detailed mechanisms of folding are not completely known, significant advances have been made in the understanding of this complex process through both experimental and theoretical approaches. In this review, the evolution of concepts from Anfinsens postulate to the new view emphasizing the concept of the energy landscape of folding is presented. The main rules of protein folding have been established from in vitro experiments. It has been long accepted that the in vitro refolding process is a good model for understanding the mechanisms by which a nascent polypeptide chain reaches its native conformation in the cellular environment. Indeed, many denatured proteins, even those whose disulfide bridges have been disrupted, are able to refold spontaneously. Although this assumption was challenged by the discovery of molecular chaperones, from the amount of both structural and functional information now available, it has been clearly established that the main rules of protein folding deduced from in vitro experiments are also valid in the cellular environment. This modern view of protein folding permits a better understanding of the aggregation processes that play a role in several pathologies, including those induced by prions and Alzheimers disease. Drug design and de novo protein design with the aim of creating proteins with novel functions by application of protein folding rules are making significant progress and offer perspectives for practical applications in the development of pharmaceuticals and medical diagnostics.

Stabilization of Taq DNA Polymerase at High Temperature by Protein Folding Pathways From a Hyperthermophilic Archaeon, Pyrococcus furiosus

“…Molecular chaperones function to restrain denatured proteins from aggregation and/or to assist protein folding (Barral et al, 2004;Hartl and Hayer-Hartl, 2002;Yon, 2001;Young et al, 2004). In this study, we used Taq DNA polymerase, an important enzyme in biotechnology (Dalton, 1999(Dalton, , 2001Pavlov et al, 2004), as a model substrate for examining the effects of chaperones on stability and durability of Taq polymerase, by incorporating chaperones into PCR reaction mixtures.…”

Over-expression and characterization of recombinant prefoldin from hyperthermophilic archaeum Pyrococcus furiosus in E. coli

“…Molecular chaperones or other stress responsive proteins would play important roles in cell tolerance, which can restrain denatured proteins from aggregation and/or assist protein folding (Hartl and HayerHartl 2002;Barral et al 2004;Yon 2001;Young et al 2004). Previous studies showed that the addition of chemical chaperones (TMAO) could promote E. coli growth at elevated temperature, even up to 46°C (Gur et al 2002;Derlinden et al 2008).…”

Formation of transitory intrachain and interchain disulfide bonds accompanies the folding and oligomerization of simian virus 40 Vp1 in the cytoplasm

“…ow proteins fold into functional, three-dimensional structures has been under intense study (1), and the folding pathways for a number of eukaryotic proteins have been characterized in vitro (2,3) or in vivo (4)(5)(6)(7)(8)(9). In the secretory pathway, protein folding is coupled to the formation and reshuffling of disulfide bonds.…”