Proteins in Wonderland: The Magical World of Pressure

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.

Liquid-Droplet-Mediated ATP-Triggered Amyloidogenic Pathway of Insulin-Derived Chimeric Peptides: Unraveling the Microscopic and Molecular Processes

“…Such high pressure sensitivity of fibrillar structures has also been observed for other amyloidogenic peptides, such as for α-synuclein and lysozyme. 35,36,39 This unusual degree to vulnerability to high hydrostatic pressure contrasts with the pressure stability of mature amyloid fibrils composed of a transthyretin fragment where Coulombic interactions play a far lesser role and the fibrils (lacking larger cavities and voids) withstand high pressure conditions exceeding 10 kbar. 42 Our observations, while untypical for some amyloid fibrils, are easily reconciled with the high content of ionic interactions stabilizing ACC 1−13 K 8 -ATP fibrils.…”

“…The application of pressure has the potential to yield additional information about the prevalent intermolecular forces underlying the aggregate formation as the balance between hydrogen bonding, electrostatic and hydrophobic intra- and intermolecular interactions can be tuned by pressure modulation. − H-bonds are generally strengthened upon pressurization, whereas salt bridges are destabilized by high pressure. The dissociation of protein aggregates and unfolding of proteins are also due to the existence of internal voids and packing defects of these structures, leading, in accordance with Le Châtelier’s principle, to an overall volume decrease upon unfolding. ,,, The abundance of ionic interactions between K n and ATP within the aggregates is expected to render them sensitive to high pressure due to the phenomenon of electrostriction ( i.e.…”

Biomolecules under Pressure: Phase Diagrams, Volume Changes, and High Pressure Spectroscopic Techniques

“…It resulted in a revolutionary new approach and allowed researchers to obtain new information about a number of biological systems [ 9 ]. Several simple model systems were studied and characterized up to now, and volumetric aspects of simple and quite complex systems have been revealed [ 10 , 11 , 12 , 13 , 14 ]. Parallel to these discoveries of basic science, practical applications were invented too, mainly in the field of food science [ 5 , 15 , 16 ].…”

Harnessing Pressure-Axis Experiments to Explore Volume Fluctuations, Conformational Substates, and Solvation of Biomolecular Systems

“…With that, the potential of volumetric and high-pressure measurements is far from being exhausted. On the contrary, it is still largely untapped in many other research areas, such as in soft condensed matter ( e.g ., colloids and polymers) chemistry and physics, supramolecular chemistry, and the nanosciences, , and many more discoveries could be made in the “Magical World of Pressure”, as Akasaka put it …”