The turn sequence directs β-strand alignment in designed β-hairpins

Abstract

A previous NMR investigation of model decapeptides with identical β-strand sequences and different turn sequences demonstrated that, in these peptide systems, the turn residues played a more predominant role in defining the type of β-hairpin adopted than cross-strand side-chain interactions. This result needed to be tested in longer β-hairpin forming peptides, containing more potentially stabilizing cross-strand hydrogen bonds and side-chain interactions that might counterbalance the influence of the turn sequence. In that direction, we report here on the design and ¹H NMR conformational study of three β-hairpin forming pentadecapeptides. The design consists of adding two and three residues at the N- and C-termini, respectively, of the previously studied decapeptides. One of the designed pentadecapeptides includes a potentially stabilizing R-E salt bridge to investigate the influence of this interaction on β-hairpin stability. We suggest that this peptide self-associates by forming intermolecular salt bridges. The other two pentadecapeptides behave as monomers. A conformational analysis of their ¹H NMR spectra reveals that they adopt different types of β-hairpin structure despite having identical strand sequences. Hence, the β-turn sequence drives β-hairpin formation in the investigated pentadecapeptides that adopt β-hairpins that are longer than the average protein β-hairpins. These results reinforce our previous suggestion concerning the key role played by the turn sequence in directing the kind of β-hairpin formed by designed peptides.