One major recent challenge in the field of life science is to understand the protein folding because many diseases involve protein misfolding. There are several ways to investigate protein structural changes. This is possible using either a physical parameter such as the temperature or chemical compounds, both perturbing the system under study.
A new approach could be high hydrostatic pressure, a physical parameter that has been recently qualified by Ernst (Nobel winner) as a invaluable tool for exploring and comprehending biological function (1). High pressure causes complete or partial denaturation of proteins because the protein-solvent system for the denatured state occupies a smaller volume than that for the native state. In a similar manner, the effect of pressure on dissociation of oligomeric proteins or nonspecific aggregates is to favor states that present a smaller specific volume. Theses affects are thought to arise from a combination of several consequences such as loss of packing defects existing in the native structure or hydration variations. Pressure perturbation dependents solely on the volume change of the system under study; in contrast, temperature involves changes in both the volume and the total energy. While denaturation by temperature is often irreversible, pressure-denaturation is, within a limited range, reversible. Consequently, hydrostatic pressure provides an elegant alternative as it induces reversible phenomenon and avoids the addition of external chemical agents.
This method has been successfully used for different pressure-induced effects, such as reversible or irreversible folding and unfolding, conformational changes with ligand binding and oligomeric dissociation. More recently, alternative prion structural changes have been revealed by high pressure.
Together with the basic concepts, all theses aspects will be evoked though specific examples.
1)Balny C, Masson P, Heremans K, BBA-PROTEIN STRUCT MOL ENZYMOL 1595, 3-10, 2002 |