Proteins in Wonderland: The Magical World of Pressure

SIMPLE SUMMARY: Unlike temperature, pH or chemical reagent, the effect of hydrostatic pressure on proteins is unique in that it controls selectively the equilibrium populations among different conformational states, without practically affecting each of their structures. Because of this unique effect of hydrostatic pressure on proteins, the application of pressure can easily manipulate the population distribution among different conformational states of a protein to a considerable extent at our will, creating what may be called “the magical world of pressure” or “the wonderland for proteins”. In this paper, we have succssfully utilized the magical world of pressure in bringing the amyloid fibrils F of wild-type hen lysozyme into the unfolded monomers U and then, upon returning to the Anfinsen regime, back into its original, natively folded state N. ABSTRACT: Admitting the “Native”, “Unfolded” and “Fibril” states as the three basic generic states of proteins in nature, each of which is characterized with its partial molar volume, here we predict that the interconversion among these generic states N, U, F may be performed simply by making a temporal excursion into the so called “the high-pressure regime”, created artificially by putting the system under sufficiently high hydrostatic pressure, where we convert N to U and F to U, and then back to “the low-pressure regime” (the “Anfinsen regime”), where we convert U back to N (U→N). Provided that the solution conditions (temperature, pH, etc.) remain largely the same, the idea provides a general method for choosing N, U, or F of a protein, to a great extent at will, assisted by the proper use of the external perturbation pressure. A successful experiment is demonstrated for the case of hen lysozyme, for which the amyloid fibril state F prepared at 1 bar is turned almost fully back into its original native state N at 1 bar by going through the “the high-pressure regime”. The outstanding simplicity and effectiveness of pressure in controlling the conformational state of a protein are expected to have a wide variety of applications both in basic and applied bioscience in the future.