Unfolding under pressure: an NMR perspective

This review aims at analysing the role of solution nuclear magnetic resonance (NMR) in pressure-induced in vitro studies of protein unfolding. Although this transition has for many years been neglected because of technical difficulties, it provides important information about the forces that keep together protein structure. We first analyse what is pressure unfolding. We then provide a critical overview of how NMR has contributed to the field and evaluate the observables used in these studies. Finally, we discuss the commonalities and differences between pressure-, cold- and heat-induced unfolding. We conclude that, while within specific peculiarities, cold and pressure denaturation both rely on the important contribution of the state of hydration of non-polar side-chains as a major factor that determines the pressure dependence of the conformational stability of proteins.