Structural Similarity between Defense Peptide from Wheat and Scorpion Neurotoxin Permits Rational Functional Design |
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| Authors: | Antonina A Berkut Dinara R Usmanova Steve Peigneur Peter B Oparin Konstantin S Mineev Tatyana I Odintsova Jan Tytgat Alexander S Arseniev Eugene V Grishin Alexander A Vassilevski |
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| Institution: | From the ‡M. M. Shemyakin and Yu. A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow 117997, Russia.;§Moscow Institute of Physics and Technology (State University), Moscow 117303, Russia.;¶Laboratory of Toxicology and Pharmacology, University of Leuven, Leuven 3000, Belgium, and ;‖N. I. Vavilov Institute of General Genetics, Russian Academy of Sciences, Moscow 119991, Russia |
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| Abstract: | In this study, we present the spatial structure of the wheat antimicrobial peptide (AMP) Tk-AMP-X2 studied using NMR spectroscopy. This peptide was 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, was engineered by incorporating the functionally important residues from κ-hefutoxin 1 onto the 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 although 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 as structural templates, which may be used for functional engineering and drug design. |
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| Keywords: | Antimicrobial Peptides Plant Defense Potassium Channels Protein Design Protein Engineering Protein Folding Hairpin Hefutoxin |
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