Evidence for an unfolding and refolding pathway in cytochrome c.

It has been suggested that three partially unfolded forms detected in a native state hydrogen exchange study of oxidized cytochrome c may represent sequential intermediates in an unfolding-refolding pathway. To better define the structure of each intermediate a 'stability labeling' method was used in which the stability of a given segment against unfolding was changed. The condition--folded or unfolded--of the stability-labeled segment in each intermediate could then be determined. The structures found are discrete and native-like and are just those necessary for a sequential pathway.