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The effects of cardiomyopathy-associated mutations in the head-to-tail overlap junction of α-tropomyosin on its properties and interaction with actinстатья
Статья опубликована в высокорейтинговом журнале
Информация о цитировании статьи получена из
Web of Science,
Scopus
Статья опубликована в журнале из списка Web of Science и/или Scopus
Дата последнего поиска статьи во внешних источниках: 2 декабря 2020 г.
- Авторы: Matyushenko A.M., Koubassova N.A., Shchepkin D.V., Kopylova G.V., Nabiev S.R., Nikitina L.V., Bershitsky S.Y., Levitsky D.I., Tsaturyan A.K.
- Журнал: International Journal of Biological Macromolecules
- Том: 125
- Год издания: 2019
- Издательство: Elsevier BV
- Местоположение издательства: Netherlands
- Первая страница: 1266
- Последняя страница: 1274
- DOI: 10.1016/j.ijbiomac.2018.09.105
- Аннотация: Tropomyosin (Tpm) plays a crucial role in the regulation of muscle contraction by controlling actin-myosin interaction. Tpm coiled-coil molecules bind each other via overlap junctions of their N- and C-termini and form a semi-rigid strand that binds the helical surface of an actin filament. The high bending stiffness of the strand is essential for high cooperativity of muscle regulation. Point mutations M8R and K15N in the N-terminal part of the junction and the A277V one in the C-terminal part are associated with dilated cardiomyopathy, while the M281T and I284V mutations are related to hypertrophic cardiomyopathy. To reveal molecular mechanism(s) underlying these pathologies, we studied the properties of recombinant Tpm carrying these mutations using several experimental approaches and molecular dynamics simulation of the junction. The M8R and K15N mutations weakened the interaction between the N- and C-termini of Tpm in the overlap junction and reduced the Tpm affinity for actin. These changes possibly led to a reduction in the regulation cooperativity. The C-terminal mutations caused only small and controversial changes in properties of Tpm and its complex with actin. Their involvement in disease phenotype is possibly caused by interaction with other sarcomere proteins.
- Добавил в систему: Цатурян Андрей Кимович