Compressibility as a Means to Detect and Characterize Globular Protein States

We report compressibility data on single-domain, globular proteins which suggest a general relationship between protein conformational transitions and Δ kSo, the change in the partial specific adiabatic compressibility which accompanies the transition. Specifically, we find transitions between native and compact intermediate states to be accompanied by small increases in kSo of +(1-4) × 10-6 cm3· g-1· bar-1 (1 bar = 100 kPa). By contrast, transitions between native and partially unfolded states are accompanied by small decreases in kSo of -(3-7) × 10-6 cm3· g-1· bar-1, while native-to-fully unfolded transitions result in large decreases in kSo of -(18-20) × 10-6 cm3· g-1· bar-1. Thus, for the single-domain, globular proteins studied here, changes in kSo correlate with the type of transition being monitored, independent of the specific protein. Consequently, kSo measurements may provide a convenient approach for detecting the existence of and for defining the nature of protein transitions, while also characterizing the hydration properties of individual protein states.