ВЫСОКОАФФИННЫЙ KV1.2-СЕЛЕКТИВНЫЙ ПЕПТИД
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Ключевые слова

Потенциал-чувствительный калиевый канал
Эпилепсия
Нейротоксин
Блокатор калиевых каналов

Как цитировать

Гиголаев, А. М., Пиньейро-Жуниор, Э. Л., Пеньёр, С., Титгат, Я., & Василевский, А. А. (2022). ВЫСОКОАФФИННЫЙ KV1.2-СЕЛЕКТИВНЫЙ ПЕПТИД. Российский физиологический журнал им. И. М. Сеченова, 108(12), 1627–1638. https://doi.org/10.31857/S0869813922120056

Аннотация

Изоформа потенциал-чувствительных калиевых каналов KV1.2 представляет интерес, поскольку мутации в ее гене ассоциированы с различными заболеваниями, например атаксией и эпилепсией. Для изучения функции KV1.2 в норме и патологии необходимы селективные лиганды. В нашей работе мы получили такой лиганд на основе известного пептидного токсина скорпиона — харибдотоксина (ChTx, α-KTx1.1) из яда Leiurus quinquestriatus — путем введения в его структуру одной аминокислотной замены M29I. Пептид ChTx_M29I был получен в бактериальной системе экспрессии. Его фармакологическая характеристика проводилась на ооцитах лягушки Xenopus laevis, экспрессирующих панель каналов KV1 человека. Было обнаружено, что по сравнению с исходным токсином пептид ChTx_M29I менее аффинен к каналам KV1.1, 1.3 и 1.6, при этом в отношении KV1.2 его активность многократно возросла. Мы связываем такой эффект со взаимодействием пептида с определенным остатком канала (V381 у KV1.2). Если в этой позиции находится сравнительно небольшой остаток, то образуется выгодный контакт, повышающий аффинность. Изученный нами пептид ChTx_M29I представляет собой один из самых высокоаффинных (со значением полумаксимальной ингибирующей концентрации ИК50 ≈ 6 пМ) и высокоселективных лигандов KV1.2 (аффинность в отношении других изоформ ниже в 680 раз и более).

https://doi.org/10.31857/S0869813922120056
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