Stabilization of partially folded states in protein folding/misfolding transitions by hydrostatic pressure

Abstract

In the last few years, hydrostatic pressure has been extensively used in the study of both protein folding and misfolding/aggregation. Compared to other chemical or physical denaturing agents, a unique feature of pressure is its ability to induce subtle changes in protein conformation, which allow the stabilization of partially folded intermediate states that are usually not significantly populated under more drastic conditions (e.g., in the presence of chemical denaturants or at high temperatures). Much of the recent research in the field of protein folding has focused on the characterization of folding intermediates since these species appear to be involved in a variety of diseasecausing protein misfolding and aggregation events. The exact mechanisms of these biological phenomena, however, are still poorly understood. Here, we review recent examples of the use of hydrostatic pressure as a tool to obtain insight into the forces and energetics governing the productive folding or the misfolding and aggregation of proteins. Correspondence

Pressure and Denaturants in the Unfolding of Triosephosphate Isomerase: The Monomeric Intermediates of the Enzymes from Saccharomyces cerevisiae and Entamoeba histolytica

“…In the study of noncovalent protein complexes formed by the association of complementary fragments (23), pressure has been shown as an alternative to characterize unfolding in the absence of chemical denaturants. Folding intermediates may be stabilized or destabilized when pressure is applied (24)(25)(26)(27); pressure promotes refolding (28)(29)(30) but in other cases leads to aggregation (31). All these apparently contradictory or unrelated effects of pressure are governed only by the volume decrease of the protein-solvent system, as predicted by Le Chatelier's principle.…”

Increased susceptibility of β‐glucosidase from the hyperthermophile Pyrococcus furiosus to thermal inactivation at higher pressures

“…Hydrostatic pressure is increasingly being used in the study of protein folding, misfolding, aggregation and transitions. In comparison with other methods of denaturation, such as temperature or chemical agents, pressure induces more subtle changes in protein conformation, allowing the stabilization of partially folded states that are often not significantly populated under more drastic conditions [15]. The inactivation plateau that indicates an intermediate state was less clear at 25 °C.…”

Highlights of the 3rd International Conference on High Pressure Bioscience and Biotechnology

“…Dr. Sérgio T. Ferreira (UFRJ, Brazil) (9) talked about the detection of metastable, partially folded intermediates in the folding and misfolding of proteins. Dr. Ferreira's group uses a combination of hydrostatic pressure, low/high temperatures and chemical denaturants to enable the detection and characterization of partially (un)folded intermediates, and has reported results on the pathways and energetics for the de novo folding of designed three-and fourhelix bundle, prion protein, and human lysozyme variants (9).…”