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Unique bell-shaped voltage-dependent modulation of Na+ channel gating by novel insect-selective toxins from the spider Agelena orientalisстатья
Статья опубликована в высокорейтинговом журнале
Информация о цитировании статьи получена из
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Статья опубликована в журнале из списка Web of Science и/или Scopus
Дата последнего поиска статьи во внешних источниках: 20 июня 2016 г.
- Авторы: Billen Bert, Vassilevski Alexander, Nikolsky Anton, Debaveye Sarah, Tytgat Jan, Grishin Eugene
- Журнал: Journal of Biological Chemistry
- Том: 285
- Номер: 24
- Год издания: 2010
- Издательство: American Society for Biochemistry and Molecular Biology Inc.
- Местоположение издательства: United States
- Первая страница: 18545
- Последняя страница: 18554
- DOI: 10.1074/jbc.m110.125211
- Аннотация: Spider venoms provide a highly valuable source of peptide toxins that act on a wide diversity of membrane-bound receptors and ion channels. In this work, we report isolation, biochemical analysis, and pharmacological characterization of a novel family of spider peptide toxins, designated β/δ-agatoxins. These toxins consist of 36–38 amino acid residues and originate from the venom of the agelenid funnel-web spider Agelena orientalis. The presented toxins show considerable amino acid sequence similarity to other known toxins such as μ-agatoxins, curtatoxins, and δ-palutoxins-IT from the related spiders Agelenopsis aperta, Hololena curta, and Paracoelotes luctuosus. β/δ-Agatoxins modulate the insect NaV channel (DmNaV1/tipE) in a unique manner, with both the activation and inactivation processes being affected. The voltage dependence of activation is shifted toward more hyperpolarized potentials (analogous to site 4 toxins) and a non-inactivating persistent Na+ current is induced (site 3-like action). Interestingly, both effects take place in a voltage-dependent manner, producing a bell-shaped curve between −80 and 0 mV, and they are absent in mammalian NaV channels. To the best of our knowledge, this is the first detailed report of peptide toxins with such a peculiar pharmacological behavior, clearly indicating that traditional classification of toxins according to their binding sites may not be as exclusive as previously assumed.
- Добавил в систему: Василевский Александр Александрович