Proteins in Wonderland: The Magical World of Pressure.

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.