The earliest events in protein folding: a structural requirement for ultrafast folding in cytochrome C.

Abstract

The folding dynamics of reduced cytochrome c (redcyt c) obtained from tuna heart, which contains a tryptophan residue at the site occupied by His33 in horse heart cytochrome c, was studied using nanosecond time-resolved optical rotatory dispersion spectroscopy. As observed previously for horse heart redcyt c, two time regimes were observed for secondary structure formation in tuna redcyt c: a fast (microseconds) and a slow (milliseconds) phase. However, the fast phase of tuna redcyt c folding was much slower and smaller in amplitude than the same phase in horse. The differences in the fast folding phases suggest that for horse heart redcyt c, the conformers that undergo the fastest observed folding have the His18-Fe-His33 heme configuration, which appears to be necessary, but not sufficient, to poise an unfolded chain conformation for fastest folding in redcyt c.