Molten globule-like state of cytochrome c under conditions simulating those near the membrane surface.

Methanol-induced conformational transitions in cytochrome c have been studied by near- and far-UV circular dichroism, Trp fluorescence, microcalorimetry, and diffusion measurements. The existence of at least two cooperative stages of transition has been shown. At the first stage, the native protein is transformed into an intermediate which has only traces of tertiary structure, but has a native-like secondary structure content and is relatively compact; i.e., it has properties of the molten globule state. On the second stage, the alcohol-induced molten globule is transformed into a more helical state, typical of proteins at high alcohol concentrations. The conditions at which the alcohol-induced molten globule exists (moderately low pH and moderately low dielectric constant) could be similar to those existing near negatively charged membrane surfaces. Consequently, these results might explain how the molten globule state can be achieved under physiological conditions.