ADIABATIC COMPRESSIBILITY OF MOLTEN GLOBULES

We report the measurement of the adiabatic compressibility beta for '' molten globule'' states of cytochrome b562 and cytochrome c. Precise d ensity and sound velocity measurements allow determination of beta in aqueous solution. Surprisingly, the molten globule apocytochrome b562 shows a beta comparable to the native holocytochrome b562. We estimate d the maximum difference in the hydration contribution to the compress ibility of apocytochrome b562 relative to holocytochrome b562 to be on ly -2.6 X 10(-11) Pa-1. Our results suggest that the intrinsic compres sibility and the overall volume fluctuations in the molten globule sta te differ only slightly from those in the native protein. With cytochr ome c we investigated the changes in beta for the transitions from the native to the acid molten globule and expanded premolten globule stat es. The molten globule at pH 2.2 was found to be somewhat ''softer'' t han the native protein at neutral pH. In contrast, a decrease in beta of the premolten globule indicates an increased penetration of water i nto the macromolecule. In both of these intermediates the differences in adiabatic compressibility relative to the native state are small in comparison to the range of adiabatic compressibility observed for dif ferent native globular proteins.