Role of cavities and hydration in the pressure unfolding of T4 lysozyme.

Pressure unfolding of proteins is a fundamental aspect of their thermodynamic response, the origins of which remain controversial. Here, we use high-pressure solution NMR to investigate the pressure response of a model protein, T4 lysozyme, under various conditions. Our data resolve longstanding controversies regarding the pressure response of this protein and the hydration of the internal hydrophobic cavity. It is shown that local packing (cavities) and the availability of conformational space have important and nonlocal impacts on the protein pressure response. Overall, the findings presented here reveal a previously unappreciated complexity in the pressure response of protein structure.