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The effects of alpha-tropomyosin Arg245Gly and Glu241Leu mutants on the structural states of actomyosin 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: Simonyan AO, Robaszkiewicz K., Borys D., Borovikov YS, Moraczewska J.J.
- Сборник: FEBS Journal
- Серия: Abstracts of 40th FEBS Congress
- Том: 282
- Тезисы
- Год издания: 2014
- Первая страница: 333
- Последняя страница: 334
- Аннотация: To investigate tropomyosin-dependent mechanisms of the actin filament activation we made two substitutions in skeletal a-tropomyosin (TM): Arg245Gly and Glu241Leu. In humans the substitutions are known to cause congenital myopathies. Using polarized fluorimetry we have studied the effects of the mutations on position of TM along filament and the spatial arrangement of actin monomers and myosin heads at various mimicked stages of the ATPase cycle in the absence of troponin. Actin, TM, and myosin subfragment-1 (S1) were fluorescently labeled and incorporated in ghost muscle fibers. The changes in polarized fluorescence during simulated stages of the ATPase cycle were measured. In the absence of S1 the mutations in TM were found to cause a movement of the TM strands towards the blocked position switching off the filament. A multi-step shift of the wild-type TM towards the actin filament centre accompanied by an increase in the number of actin subunits switched into the “on” state, as well as the number of S1 in the strong-binding state was observed. At all stages of the ATPase cycle the Arg245Gly and Glu241Leu mutations captured TM strands near the blocked position, decreased the number of actin monomers in the “on” state, but increased the number of S1 in the strong-binding state. We concluded that mutations-associated changes in TM structure interfere with the cross-bridge cycle by slowing down the rate of S1 release from actin. This mechanism may be responsible for the muscle weakness observed in patients. The work was supported by the RFBR (No14-04-00454 and 14-04-31527).
- Добавил в систему: Боровиков Юрий Сергеевич