Structural similarity between defense peptide from wheat and scorpion neurotoxin permits rational functional design.

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 ?-helical hairpin fold and therefore belongs to the ?-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 ?-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 ?m) to ?-hefutoxin 1 (IC50 ? 40 ?m). We conclude that ?-hairpinins are attractive in their simplicity as structural templates, which may be used for functional engineering and drug design.

SUBMITTER: Berkut AA 

PROVIDER: S-EPMC4022899 | biostudies-literature | 2014 May

REPOSITORIES: biostudies-literature