Molecular Determinants of Temperature Dependence of Protein Volume Change upon Unfolding

Pressure is a well-known environmental stressor that can either stabilize or destabilize proteins. The volumetric change upon protein unfolding determines the effect of pressure on protein stability, where negative volume changes destabilized proteins at high pressures. High temperature often accompanies high pressure, for example, in the ocean depths near hydrothermal vents or near faults, so it is important to study the effect of temperature on the volumetric change upon unfolding. We previously detailed the magnitude and sign of the molecular determinants of volumetric change, allowing us to quantitatively predict the volumetric change upon protein unfolding. Here, we present a comprehensive analysis of the temperature dependence of the volumetric components of proteins, showing that hydration volume is the primary component that defines expansivities of the native and unfolded states and void volume only contributes slightly to the folded state expansivity.