A short linear peptide derived from the N-terminal sequence of ubiquitin folds into a water-stable non-native beta-hairpin.

A 16-residue peptide derived from the N-terminal sequence of ubiquitin forms a stable monomeric beta-hairpin that is estimated to be approximately 80% populated in aqueous solution. The peptide sequence has been modified from native ubiquitin by replacing the five residues found in a type I G1 bulged turn (Thr-Leu-Thr-Gly-Lys) with four residues (Asn-Pro-Asp-Gly) to maximize the probability of forming a beta-turn. Unexpectedly, the bulged turn conformation is re-established in the beta-hairpin in solution with two consequences: a one-amino acid frameshift in the alignment of the peptide main chain occurs relative to the native hairpin, and side chains formerly on opposite faces of the hairpin are brought together on the same face. The presence of the bulged turn in native ubiquitin may help in the avoidance of the stable non-native register of amino acids found here which would be unproductive for folding.