It has been suggested that three partially unfolded forms detected in
a native state hydrogen exchange study of oxidized cytochrome c may re
present sequential intermediates in an unfolding-refolding pathway. To
better define the structure of each intermediate a 'stability labelin
g' method was used in which the stability of a given segment against u
nfolding was changed. The condition - folded or unfolded - of the stab
ility-labeled segment in each intermediate could then be determined. T
he structures found are discrete and native-like and are just those ne
cessary for a sequential pathway.