Solution structure of agelenin, an insecticidal peptide isolated from the spider Agelena opulenta, and its structural similarities to insect-specific calcium channel inhibitors

• Published in: FEBS letters 2007-08, Vol.581 (20), p.3789-3794
• Main Authors: Yamaji, Nahoko, Sugase, Kenji, Nakajima, Terumi, Miki, Takafumi, Wakamori, Minoru, Mori, Yasuo, Iwashita, Takashi
• Format: Article
• Language: English
• Subjects: 50% paralytic dose; Agelenidae; Agelenin; Amino Acid Sequence; Animals; Araneae; Arginine - chemistry; Calcium Channel Blockers - pharmacology; Cell Line; Disulfides - chemistry; Dose-Response Relationship, Drug; double-quantum-filtered correlation spectroscopy; DQF-COSY; Gryllidae - drug effects; Humans; hydrogen–deuterium exchange; H–D exchange; ICK; inhibitor cystine knot; Insect calcium channel; Insecticides - chemistry; Insecticides - metabolism; Insecticides - pharmacology; Kinetics; Models, Molecular; Molecular Sequence Data; NMR; NOESY; nuclear magnetic resonance; Nuclear Magnetic Resonance, Biomolecular; nuclear Overhauser effect spectroscopy; Patch-Clamp Techniques; PD50; Peptides - chemistry; Peptides - isolation & purification; Peptides - metabolism; Peptides - pharmacology; Phenylalanine - chemistry; Protein Binding; Protein Conformation; Protein Structure, Secondary; RMSD; root-mean-square deviation; Sequence Homology, Amino Acid; Serine - chemistry; Spider toxin; Spider Venoms - chemistry; Spider Venoms - isolation & purification; Spider Venoms - metabolism; Spider Venoms - pharmacology; Spiders - chemistry; Structure; TOCSY; total correlation spectroscopy; ω-ACTX-Hv1a; ω-ACTX-Hv2a; ω-Aga-IVA; ω-agatoxin-IVA; ω-atracotoxin-Hv1a; ω-atracotoxin-Hv2a
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/j.febslet.2007.06.077

Agelenin, isolated from the Agelenidae spider Agelena opulenta, is a peptide composed of 35 amino acids. We determined the three-dimensional structure of agelenin using two-dimensional NMR spectroscopy. The structure is composed of a short antiparallel β-sheet and four β-turns, which are stabilized by three disulfide bonds. Agelenin has characteristic residues, Phe9, Ser28 and Arg33, which are arranged similarly to the pharmacophore of the insect channel inhibitor, ω-atracotoxin-Hv1a. These observations suggest that agelenin and ω-atracotoxin-Hv1a bind to insect calcium channels in a similar manner. We also suggest that another mode of action may operate in the channel inhibition by ω-agatoxin-IVA and ω-atracotoxin-Hv2a.