Kinetic studies of the early events in cytochrome c folding are reviewed with a focus on the evidence for folding intermediates on the submillisecond timescale. Evidence from time-resolved absorption, circular dichroism, magnetic circular...
moreKinetic studies of the early events in cytochrome c folding are reviewed with a focus on the evidence for folding intermediates on the submillisecond timescale. Evidence from time-resolved absorption, circular dichroism, magnetic circular dichroism, fluorescence energy and electron transfer, small-angle X-ray scattering and amide hydrogen exchange studies on the t < or = 1 ms timescale reveals a picture of cytochrome c folding that starts with the approximately 1-micros conformational diffusion dynamics of the unfolded chains. A fractional population of the unfolded chains collapses on the 1 - 100 micros timescale to a compact intermediate I(C) containing some native-like secondary structure. Although the existence and nature of I(C) as a discrete folding intermediate remains controversial, there is extensive high time-resolution kinetic evidence for the rapid formation of I(C) as a true intermediate, i.e., a metastable state separated from the unfolded state by a discrete free e...