Effects of turn residues in directing the formation of the beta-sheet and in the stability of the beta-sheet

The designed peptide (denoted 20-mer, sequence VFITS(D)PGKTYTEV(D)PGOKILQ) has been shown to form a three-strand antiparallel beta -sheet. It is gener ally believed that the (D)Pro-Gly segment has the propensity to adopt a typ e II ' beta -turn, thereby promoting the formation of this beta -sheet. Her e, we replaced (D)Pro-Gly with Asp-Gly, which should favor a type I ' turn, to examine the influence of different type of turns on the stability of th e beta -sheet. Contrary to our expectation, the mutant peptide, denoted P6D , forms a five-residue type I turn plus a beta -bulge between the first two strands due to a one amino-acid frameshift in the hydrogen bonding network and side-chain inversion of the first beta -strand. In contrast, the same kind of substitution at (D)Pro-14 in the double mutant, denoted P6DP14D, do es not yield the same effect. These observations suggest that the SDGK sequ ence disfavors the type I ' conformation while the VDGO sequence favors a t ype I ' turn, and that the frameshift in the first strand provides a way fo r the peptide to accommodate a disfavored turn sequence by protruding a bul ge in the formation of the beta -hairpin. Thus, different types of turns ca n affect the stability of a beta -structure.