Applications of pressure perturbation calorimetry to study factors contributing to the volume changes upon protein unfolding

Abstract

BackgroundPressure perturbation calorimetry (PPC) is a biophysical method that allows direct determination of the volume changes upon conformational transitions in macromolecules. Scope of this reviewThis review provides novel details of the use of PPC to analyze unfolding transitions in proteins. The emphasis is made on the data analysis as well as on the validation of different structural factors that define the volume changes upon unfolding. Four case studies are presented that show the application of these concepts to various protein systems. Major conclusionsThe major conclusions are:1.Knowledge of the thermodynamic parameters for heat induced unfolding facilitates the analysis of the PPC profiles.2.The changes in the thermal expansion coefficient upon unfolding appear to be temperature dependent.3.Substitutions on the protein surface have negligible effects on the volume changes upon protein unfolding.4.Structural plasticity of proteins defines the position dependent effect of amino acid substitutions of the residues buried in the native state.5.Small proteins have positive volume changes upon unfolding which suggests difference in balance between the cavity/void volume in the native state and the hydration volume changes upon unfolding as compared to the large proteins that have negative volume changes. General significanceThe information provided here gives a better understanding and deeper insight into the role played by various factors in defining the volume changes upon protein unfolding. This article is part of a Special Issue entitled Microcalorimetry in the BioSciences — Principles and Applications, edited by Fadi Bou-Abdallah.