Liquid-like state of side chains at the intermediate stage of protein denaturation

We propose a model for a conformational state of a partially denatured protein molecule which we call CMG (Compact Molten Globule) state. The CMG state is one where the freedom of motion of side chains is released while that of the backbone chain is restricted as in the native state; In other words, it is the state of fixed psi and phi, but of free chi in terms of the dihedral angles of the polypeptide chain. Experimental results of our study on the denatured state of cytochrome c in pH 2, 0.5 M KCl (IIb state) and those in the report of Dolgikh et al. (1981) on acid denatured state (A state) of alpha-lactalbumin support the present model. In IIb state, the 360 MHz 1H-NMR spectrum is similar to that of the fully denatured state, while intrinsic viscosity and diffusion coefficient are close to the native state. A diagram of the internal phase of cytochrome c in the course of acid denaturation is given, and discussions are presented as to whether this molten globule state might be comprehensively applied to other proteins.