Structure of a simplified β-hairpin and its ATP complex.

The capacity of three designed duodecamer peptides with the low diversity sequence: H1ϕ2I3K4I5D6G7K8ϕ9I10K11H12 where ϕ is His, Phe or Trp, to adopt a β-hairpin conformation was studied using NMR spectroscopy. Whereas KIAβH, the variant with His at positions two and nine, is disordered, KIAβF, the peptide with Phe at these positions, adopts a small population of β-hairpin. A high population of β-hairpin structure was detected for KIAβW, the variant with Trp. Utilizing NMR data, the structure of KIAβW was solved and it reveals a β-hairpin stabilized by hydrophobic interactions between Ile residues on one face and Trp-Trp and cation-π interactions on the opposite face. Upon adding ATP, these peptides show chemical shift changes indicative of ATP binding. The binding of ATP to KIAβW shows a KD ≈ 20 μM at pH 5, 5 °C and has a 1:1 stoichiometry. The KIAβW-ATP complex was determined using NMR spectroscopy and reveals the adenine ring sandwiched between the two Trp indole rings and that ATP binding induces important conformational changes in His1, Trp2, Lys4, Trp9 and Lys11 in the β-hairpin. The implications of these results for the hypothetic presence of β-hairpins and amyloids alongside RNAs on the prebiotic Earth are discussed.