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Spatial structure, analgesic effects, and TRPA1 modulation of the Kunitz-type sea-anemone peptide HCIQ2C1статья
Информация о цитировании статьи получена из
Scopus
Статья опубликована в журнале из списка Web of Science и/или Scopus
Дата последнего поиска статьи во внешних источниках: 9 октября 2024 г.
- Авторы: Lyukmanova Ekaterina, Kulbatskii D.S., Mironov P.A., Oreshkov S.D., Paramonov A.S., Menshov A.S., Kvetkina A.N., Klimovich A.A., Pislyagin E.A., Leichenko E.V., Shenkarev Z.O.
- Журнал: Toxicon : official journal of the International Society on Toxinology
- Том: 248
- Год издания: 2024
- Издательство: Pergamon Press
- Местоположение издательства: United States
- Номер статьи: 107905
- DOI: 10.1016/j.toxicon.2024.107905
- Аннотация: HCIQ2c1 peptide is a member of a large serine protease inhibitor family isolated from the sea anemone Heteractis crispa venom. HCIQ2c1 inhibits trypsin and other serine proteinases, affects P2X7R receptors, but does not modulate TRPV1 channel. Here, spatial structure and dynamics of recombinant HCIQ2c1 was determined by 1H-15N NMR spectroscopy. The HCIQ2c1 molecule involves three-stranded antiparallel β-sheet (Phe19–Asp25, Lys30–Tyr36, and Asn45–Phe46) and C-terminal α-helix (Leu49–Arg57) arranged in the conventional α+β Kunitz-type fold stabilized by three disulfides. Two loops L1 and L2 (Val12–Gly17 and Gly37–Asn42) demonstrate high mobility on μs-ms time scale. The L1-loop exposed to solution contains a reactive site for serine proteases, including the Arg16–Gly17 peptide bond resistant to proteolytic attack. Probably, the high flexibility of L-loops is important for the HCIQ2c1 inhibitory activity. The HCIQ2c1 molecule exhibits weak amphipathic properties with a predominance of positive charge on the molecular surface. In vivo capsaicin and AITC tests in a mouse model revealed the analgesic and anti-inflammatory effect of HCIQ2c1, while no neurotropic and neurotoxic effects were observed. HCIQ2c1 was found to potentiate both inward and outward currents through rat TRPA1 channel evoked either by covalent agonist AITC or by non-covalent agonist diclofenac. Incubation of the oocytes expressing TRPA1 with HCIQ2c1 up to 20 min haven't changed the sign of modulatory effect, indicating that the analgesic properties are likely to be manifested through sensory neuron desensitization induced by prolonged receptor potentiation.
- Добавил в систему: Миронов Павел Андреевич