Structure of a paralytic peptide from an insect, Manduca sexta

Paralytic peptide 1 (PP1) from a moth, Manduca sexta, is a 23-residue pepti de (Glu-Asn-Phe-Ala-Gly-Gly-Cys-Ala-Thr-Gly-Tyr-Leu-Arg-Thr-Ala-Asp-Gly-Arg -Cys-Lys-Pro-Thr-Phe) that was first found to have paralytic activity when injected into M. sexta larvae. Recent studies demonstrated that PP1 also st imulated the spreading and aggregation of a blood cell type called plasmato cytes and inhibited bleeding from wounds. We determined the solution struct ure of PP1 by two-dimensional H-1 NMR spectroscopy to begin to understand s tructural-functional relationships of this peptide. PP1 has an ordered stru cture, which is composed of a short antiparallel beta-sheet at residues Tyr (11)-Thr(14) and Arg(18)-Pro(21), three beta turns at residues Phe(3)-Gly(6 ), Ala(8)-Tyr(11) and Thr(14)-Gly(17), and a half turn at the carboxyl-term inus (residues Lys(20)-Phe(23)). The well-defined secondary and tertiary st ructure was stabilized by hydrogen bonding and side-chain hydrophobic inter actions. In comparison with two related insect peptides, whose structures h ave been solved recently, the amino-terminal region of PP1 is substantially more ordered. The short antiparallel beta-sheet of PP1 has a folding patte rn similar to the carboxyl-terminal subdomain of epidermal growth factor (E GF). Therefore, PP1 may interact with EGF receptor-like molecules to trigge r its different biological activities.