Sea Anemone Peptide with Uncommon β-Hairpin Structure Inhibits Acid-sensing Ion Channel 3 (ASIC3) and Reveals Analgesic Activity
作者： Dmitry I. Osmakov , Sergey A. Kozlov , Yaroslav A. Andreev , Sergey G. Koshelev , Nadezhda P. Sanamyan
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摘要: Abstract Three novel peptides were isolated from the venom of sea anemone Urticina grebelnyi. All them are 29 amino-acid crosslinked by two disulfide bridges, with a primary structure similar to other belonging structural group 9a. The gene encoding shared precursor protein identified was determined. One peptide, π-AnmTX Ugr 9a-1 (short name 9-1), produced reversible inhibition effect on both transient and sustained current human ASIC3 channels expressed in Xenopus laevis oocytes. It completely blocked component (IC50 10 +/- 0.6 μM) partially (48 2%) inhibited amplitude 1.44 0.19 μM). In vivo tests mice, 9-1 significantly reversed inflammatory acid-induced pain. peptides, AnmTX 9a-2 (Ugr 9-2) 9a-3 9-3), did not inhibit current. NMR spectroscopy revealed that has an uncommon spatial structure, stabilized S-S three classical β-turns twisted β-hairpin without interstrand bonds. This is peptide which we propose boundless β-hairpin.
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