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Structural basis for the transmembrane signaling and antidepressant-induced activation of the receptor tyrosine kinase TrkBстатья
Статья опубликована в высокорейтинговом журнале
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: 1 января 2025 г.
- Авторы: Kot Erik F., Goncharuk Sergey A., Franco María Luisa, McKenzie Daniel M., Arseniev Alexander S., Benito-Martínez Andrea, Costa Mario, Cattaneo Antonino, Hristova Kalina, Vilar Marçal, Mineev Konstantin S.
- Журнал: Nature communications
- Том: 15
- Номер: 1
- Год издания: 2024
- Издательство: Nature Pub. Group
- Местоположение издательства: United Kingdom
- Номер статьи: 9316
- DOI: 10.1038/s41467-024-53710-7
- Аннотация: Neurotrophin receptors of the Trk family are involved in the regulation of brain development and neuroplasticity, and therefore can serve as targets for anti-cancer and stroke-recovery drugs, antidepressants, and many others. The structures of Trk protein domains in various states upon activation need to be elucidated to allow rational drug design. However, little is known about the conformations of the transmembrane and juxtamembrane domains of Trk receptors. In the present study, we employ NMR spectroscopy to solve the structure of the TrkB dimeric transmembrane domain in the lipid environment. We verify the structure using mutagenesis and confirm that the conformation corresponds to the active state of the receptor. Subsequent study of TrkB interaction with the antidepressant drug fluoxetine, and the antipsychotic drug chlorpromazine, provides a clear self-consistent model, describing the mechanism by which fluoxetine activates the receptor by binding to its transmembrane domain.
- Добавил в систему: Кот Эрик Федорович