Turn residue sequence determines beta-hairpin conformation in designed peptides

A series of linear peptides designed to fold into different beta-hairpin conformations in aqueous solution has been studied by H-1 NMR with the aim of understanding the role played by the turn residue sequence in defining beta-hairpin structure. The designed peptides differ only in the amino acid sequence of the putative turn region and have identical strand residues. Our results clearly demonstrate that the turn residue sequence determines the turn conformation and, thereby, other features of the beta-hairpin conformation, such as the pattern of interstrand residue pairing and the type of hydrogen-bonding register between beta-strand backbone atoms. Furthermore, two key structural factors responsible for the stability of different types of turns were identified. Thus, a side-chain-side-chain interaction between Asn at position i and Thr at position i + 4 stabilizes five-residue turns, whereas a four-residue turn is stabilized when the first residue of the turn has high tendency to populate the alpha(R) region of the Ramachandran map. Our results highlight the relevance of turn structures in the early events of protein folding.