Hierarchical folding of cytochrome c


nature structural biology • volume 7 number 6 • june 2000 443 To catch a glimpse of the complete molecular picture of a protein folding reaction is one of the major challenges for protein chemists. A central problem lies in clarification of the early folding events. Several lines of evidence suggest that the initial step in protein folding involves the collapse of a polypeptide chain1. However, it is unclear whether the collapse is accompanied by or preceded by any secondary and/or tertiary structure formation — does secondary structure form first and guide the formation of the tertiary structure? If a structure forms early in the folding process, is it always native-like or could it contain nonnative elements (misfolded structures)? If wrong structural elements form, would they retard or accelerate the subsequent folding events? Are these processes different for each protein or are there general rules that are common to all proteins? On page 514 of this issue, Akiyama et al.2 address these questions by probing the formation of secondary structure in the folding reaction of cytochrome c in the submillisecond time scale with circular dichroism (CD). These new results show that the early folding intermediate of cytochrome c consists of ~20% of the native α-helical structure and is insensitive to the refolding conditions. The authors also show that the majority of the secondary structure is established after the early collapse of the polypeptide chain with a time constant of ∼500 μs. These results together with previous observations in the literature suggest that the bottleneck for the folding reaction of cytochrome c originates from the final search for the native structure rather than from the initial condensation of the polypeptide chain. This elegant work reported by Akiyama et al.2 not only advances our understanding of the early folding events of cytochrome c, but also provides a new tool for future investigations of other protein systems.

DOI: 10.1038/nsb0600_443


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@article{Yeh2000HierarchicalFO, title={Hierarchical folding of cytochrome c}, author={S R Yeh and Denis L . Rousseau}, journal={Nature Structural Biology}, year={2000}, volume={7}, pages={443-445} }