БИОХИМИЯ, 2022, том 87, вып. 3, с. 400–418

УДК 577.112.7;617.741

Агрегация белков при катаракте: роль возрастных модификаций и мутаций α‑кристаллинов*

Обзор

© 2022 P. Budnar, R. Tangirala, R. Bakthisaran, Ch.M. Rao **mohan@ccmb.res.in; mohan.ccmb@gmail.com

Centre for Cellular and Molecular Biology (CCMB), Council of Scientific and Industrial Research (CSIR), Uppal Road, Hyderabad 500007, India

Поступила в редакцию 05.10.2021
После доработки 02.02.2022
Принята к публикации 02.02.2022

DOI: 10.31857/S0320972522030071

КЛЮЧЕВЫЕ СЛОВА: катаракта, агрегация, α‑кристаллин.

Аннотация

Катаракта является основной причиной слепоты. Из‑за нарушения процесса обновления белков в хрусталике глаза накапливаются возрастные и экологические модификации белков, которые изменяют их нативную конформацию, что приводит к образованию склонных к агрегации промежуточных продуктов, а также нерастворимых и светорассеивающих агрегатов, снижающих прозрачность хрусталика. Белок хрусталика, α‑кристаллин, является молекулярным шапероном, который предотвращает агрегацию белка, тем самым поддерживая прозрачность хрусталика. Однако мутации или посттрансляционные модификации, такие как окисление, деамидирование, усечение и перекрёстные сшивки, могут сделать α‑кристаллины неэффективными и привести к обострению болезни. В настоящей работе нами описаны такие мутации и изменения, а также их последствия. Возрастные модификации α‑кристаллинов влияют на их структуру, олигомеризацию и шаперонную функцию. Мутации α‑кристаллинов могут привести к агрегации/внутриклеточным включениям, связанным с нарушением структуры и сборки олигомеров, что приводит к перестройке областей, склонных к агрегации. Такие структурные перестройки могут привести к обнажению до сих пор скрытых участков, склонных к агрегации, тем самым заполняя склонное к агрегации состояние (-я) и облегчая аморфную/амилоидную агрегацию и/или несоответствующие взаимодействия с клеточными компонентами. Изучение вызванных мутациями изменений в структуре, сборке олигомеров, механизмах агрегации и интерактомах α‑кристаллинов будут полезны в борьбе с заболеваниями, связанными с агрегацией белков.

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Сноски

* Статья опубликована в рамках специального выпуска «Неправильный фолдинг и агрегация белков при катаракте» (том 87, № 2, 2022).

** Адресат для корреспонденции.

Конфликт интересов

Авторы заявляют об отсутствии конфликта интересов.

Соблюдение этических норм

Настоящая статья не содержит описания каких-либо исследований с участием людей или животных в качестве объектов.

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