БЕЛКИ-ТРАНСПОРТЕРЫ ОРГАНИЧЕСКИХ КАТИОНОВ СЕМЕЙСТВА SLC22 (OCT-OCTN). МОЛЕКУЛЯРНОЕ РАЗНООБРАЗИЕ, СТРУКТУРА, ФУНКЦИЯ, УЧАСТИЕ В ФУНКЦИОНИРОВАНИИ СИСТЕМЫ МЕЖОРГАННОЙ КОММУНИКАЦИИ У ЖИВОТНЫХ (ОБЗОР)

Лев Павлович Смирнов, Lev Smirnov

Аннотация


В состав семейства SLC22 кроме транспортеров органических анионов (ОАТ) включены транспортеры органических катионов (ОСТ) и карнитин/цвиттер-ионов (OCTN). К настоящему времени идентифицировано 3 транспортера органических катионов ОСТ1, 2, 3, а также 3 транспортера карнитин/цвиттер-ионов OCT6, OCTN1 и OCTN2. Субстраты OCT это структурно разнообразные экзогенные соединения (включая некоторые тяжелые металлы), а также ряд эндогенных веществ. ОСТ сходны по своей структуре с другими белками суперсемейства MFS. Они состоят из 543 - 557 аминокислот, которые формируют 12 трансмембранных спиралей (доменов). Эти домены организованы как N- и C-концевые упаковки из 6 спиралей. Большая внеклеточная петля между первым и вторым доменами (110 аминокислотных остатков) содержит три сайта N гликозилирования и 6 консервативных остатков цистеина. Большая внутриклеточная петля, связывающая спирали 6 и 7 имеет множественные сайты фосфорилирования, медиаторами которого выступают протеинкиназы A, C, G, казеин киназа 2. Некоторые особенности являются уникальными для сочленов семейства SLC22, например, специфическая последовательность [-Сер/Tре]-Иле-Вал-Тре-Глу-[Фен/Три]-[Асп/Асн]-Лей-Вал-Цис- перед спиралью 2. OCT1 и OCT2 сходны на 70% процентов по аминокислотному составу и примерно на 50% с OCT3. Транспортеры семейств SLC (импортеры) и ABC (ATP-binding cassette, экспортеры), экспрессируемые в барьерном эпителии, служащем интерфейсом для жидких компартментов в органах, таких как, мозг, глаза, уши, печень и почки совместно участвуют в обработке большого числа циркулирующих эндогенных метаболитов и/или токсинов.

 


Ключевые слова


ОСТ; OCTN; переносчики органических катионов; субстратная специфика; межорганная коммуникация

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Литература


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DOI: http://dx.doi.org/10.17076/eb866

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