Structural Similarity between Defense Peptide from Wheat and Scorpion Neurotoxin Permits Rational Functional Design
Berkut, Antonina A × Usmanova, Dinara R Peigneur, Steve Oparin, Peter B Mineev, Konstantin S Odintsova, Tatyana I Tytgat, Jan Arseniev, Alexander S Grishin, Eugene V Vassilevski, Alexander A #
American Society for Biochemistry and Molecular Biology
Journal of Biological Chemistry vol:289 issue:20 pages:14331-40
In this paper we present the spatial structure of the wheat antimicrobial peptide (AMP) Tk-AMP-X2 studied using NMR spectroscopy. This peptide is found to adopt a disulfide-stabilized α-helical hairpin fold and therefore belongs to the α-hairpinin family of plant defense peptides. Based on Tk-AMP-X2 structural similarity to cone snail and scorpion potassium channel blockers, a mutant molecule Tk-hefu and was engineered by incorporating the functionally important residues from κ-hefutoxin 1 onto Tk-AMP-X2 scaffold. The designed peptide contained the so-called essential dyad of amino acid residues significant for channel-blocking activity. Electrophysiological studies showed that while the parent peptide Tk-AMP-X2 did not present any activity against potassium channels, Tk-hefu blocked Kv1.3 channels with similar potency (IC50 ≈35 μM) to κ-hefutoxin 1 (IC50 ≈40 μM). We conclude that α-hairpinins are attractive in their simplicity structural templates, which may be used for functional engineering and drug design.