ABSTRACT
The turns joining segments of secondary structure have been proposed to be key elements in dictating the folded structures of native proteins. An alternative view assumes that turns play a passive role and are merely default structures that occur as a consequence of interactions between antiparallel segments of secondary structure, with chain reversal being dictated by the context surrounding the turn and not by the sequence of the turn itself. The solvent-exposure of turns and their tolerance to evolutionary variance suggests that they may have little or no effect on the formation of native structures. Previous investigations have focused on various types of beta-turns that connect antiparallel beta-strands with comparatively little reported on the structural role of interhelical turns. Here we probe the structural importance of such a turn in an antiparallel 4-helix bundle by randomly substituting an interhelical tripeptide in cytochrome b-562 with many different amino-acid sequences. Thirty-one of the resulting substituted proteins were characterized and all of them were shown to fold into stable, native-like structures. These results suggest that this interhelical turn does not does not play a dominant role in determining the folded structure of this antiparallel 4-helix bundle.
