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Abnormal movement of mutant β-tropomyosin associated with congenital myopathy causes aberrant response of myosin heads and actin during the ATPase cycleтезисы доклада
Информация о цитировании статьи получена из
Web of Science
Дата последнего поиска статьи во внешних источниках: 7 сентября 2017 г.
- Авторы: Avrova S.V., Rysev N.A., Karpicheva O., Simonyan A., Chernev A., Piers A., Redwood C., Borovikov Y.S.
- Сборник: Journal of Muscle Research and Cell Motility
- Серия: Abstracts of 43rd European muscle conference, Salzburg, Austria
- Том: 36
- Тезисы
- Год издания: 2015
- Место издания: Springer Salzburg, Austria
- Первая страница: 78
- Последняя страница: 78
- DOI: 10.1007/s10974-015-9407-3
- Аннотация: We have investigated how the b-TM mutations R91G, E139del, and E41K that cause congenital myopathy affect TM’s position on the thin filament and the spatial arrangement of actin monomers and myosin heads during the ATPase cycle. We labeled recombinant wild-type and mutant TMs with 5-IAF, S1 with 1.5-IAEDANS and F-actin with FITC-phalloidin, incorporated them into troponin-free ghost muscle fibres and measured polarized fluorescence at different stages of the ATPase cycle. It was found that the position of wild-type TM was correlated with the position and conformational state of the myosin heads and actin monomers at all the intermediate stages of the ATPase cycle, and each of the mutations uncoupled this relationship. The R91G mutation shifted TM strands further to the centre of the filaments, increased the proportion of the switched on actin monomers during strong binding between actin and myosin. During weak-binding, the R91G mutation, on the contrary, shifted TM strands further to the periphery of the filaments and decreased the proportion of the switched on actin monomers. In addition, the R91G mutation increased the number of myosin heads in the strong-binding states at all intermediate stages of the cycle. The E139del mutation stabilized TM strands near the filament centre during the ATPase cycle, and decreased the number of the switched on actin monomers and myosin heads in the strong-binding states. The E41K stabilized TM strands near the filament periphery during the ATPase cycle and increased the amount of the myosin heads in the strong-binding states during relaxation. It is suggested that the aberrant TM movement causes abnormal response of the contractile system, resulting in contracture and muscle weakness. This work was supported by the Russian Fund for Fundamental Research (Grants No. 14-04-00454a, 14-04-31527a), the Program of Presidium of RAS (theme No. 7) and the Muscular Dystrophy Campaign.
- Добавил в систему: Карпичева Ольга Евгеньевна