Effects of turn residues in directing the formation of the β-sheet and in the stability of the β-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 generally believed that the (D)Pro-Gly segment has the propensity to adopt a type II ' beta -turn, thereby promoting the formation of this beta -sheet. Here, 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 the 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, does not yield the same effect. These observations suggest that the SDGK sequence disfavors the type I ' conformation while the VDGO sequence favors a type I ' turn, and that the frameshift in the first strand provides a way for the peptide to accommodate a disfavored turn sequence by protruding a bulge in the formation of the beta -hairpin. Thus, different types of turns can affect the stability of a beta -structure.