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^DPGKTYTEV^DPGOKILQ) has been shown to form a three‐strand antiparallel β‐sheet. It is generally believed that the ^DPro‐Gly segment has the propensity to adopt a type II′ β‐turn, thereby promoting the formation of this β‐sheet. Here, we replaced ^DPro‐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 β‐sheet. Contrary to our expectation, the mutant peptide, denoted P6D, forms a five‐residue type I turn plus a β‐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 β‐strand. In contrast, the same kind of substitution at ^DPro‐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 β‐hairpin. Thus, different types of turns can affect the stability of a β‐structure.