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The effect of the arthrogryposis-causingArg91Gly mutation in beta-skeletaltropomyosin on its position on the thinfilament and flexibility during the ATPasecycleтезисы доклада
Информация о цитировании статьи получена из
Web of Science
Дата последнего поиска статьи во внешних источниках: 7 сентября 2017 г.
- Авторы: Simonyan A., Rysev N., Chernev A., Krutetskaya Z., Piers A., Redwood C., Borovikov Y.
- Сборник: FEBS Journal
- Серия: Abstracts of 38th FEBS Congress
- Том: 280
- Тезисы
- Год издания: 2013
- Первая страница: 158
- Последняя страница: 158
- Аннотация: Previous studies have shown that the distal arthrogryposis-causing Arg91Gly mutation in b-tropomyosin (TM) alters contractile regulation. To investigate how the substitution of residue Arg91of b-TM with a Gly residue affects the position and flexibility of TMs on the thin filaments, we labelled recombinant wild type and mutant b-TMs with 5-IAF and F-actin with FITC-phalloidin and incorporated them into the ghost muscle fibres. The orientation and mobility of the probes were studied by polarized fluorimetry at different stages of the ATPase cycle. Multistep alterations in the position and flexibility of b-TM strands and actin monomers in the thin filaments during the ATPase cycle were observed. In the thin filaments the flexural rigidity of Factin was more than twice lower than the rigidity of either of TMs. In the absence of myosin heads the mutation in TM was found to transfer tropomyosin strands towards the inner domain of actin, exposing more myosin-binding sites. Myosin heads shift the mutant TM further towards the open position, markedly changing the flexural rigidity of F-actin and TM strands and switch actin monomers on. This indicates that the amount of strongly bound cross-bridges increases at all the mimicked stages of the ATPase cycle. These structural changes in the thin filament are likely to underlie the observed rise in Ca2+-sensitivity caused by this mutation, which initiates the disease remodeling. The work was supported by the Russian Foundation for Basic Research (№ 11-04-00244a), the Programme of Presidium of RAS (theme № 7) and the Muscular Dystrophy Campaign.
- Добавил в систему: Боровиков Юрий Сергеевич