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Distal arthrogryposis-associated Arg91Gly mutation in btropomyosin induces the structural changes in the thin filaments during the atpase cycleтезисы доклада
Информация о цитировании статьи получена из
Scopus
Дата последнего поиска статьи во внешних источниках: 7 сентября 2017 г.
- Авторы: Simonyan A.H., Rysev N.A., Chernev A.A., Piers A., Redwood C.S., Borovikov Y.S.
- Сборник: Journal of Muscle Research and Cell Motility
- Серия: Abstracts of 42nd European muscle conference, Amsterdam
- Том: 35
- Тезисы
- Год издания: 2014
- Издательство: SPRINGER
- Местоположение издательства: VAN GODEWIJCKSTRAAT 30, DORDRECHT, NETHERLANDS, 3311GZ
- Первая страница: 120
- Последняя страница: 120
- DOI: 10.1007/s10974-014-9384-y
- Аннотация: The distal arthrogryposis (DA) is a serious congenital disease characterized by various muscle deformities and contractures of distal limbs such as hands and feet. Mutations in the three genes TPM2, TNNT3, and TNNI2 were identified at the pathogenesis of DA. The aim of the present study has been to investigate the effect of Arg91Gly point mutation in b-tropomyosin (b-Tm) molecule from skeletal muscles on its position and flexibility in the thin filaments. For this purpose the fluorescent probes, FITC-phalloidin and 5-IAF, specifically bound to F-actin and mutant b-Tm, respectively in the ghost muscle fibers (GF) were used. The Arg91Gly mutation in TPM2, encoding skeletal b-tropomyosin associated with DA has been investigated by the method of polarized fluorimetry. During experiments the spatial orientation and mobility of the probes at several simulated stages of ATP hydrolysis cycle were assessed. In the thin filaments the flexural rigidity of F-actin was less than half 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. Incorporation of myosin heads (S1) into the GF causes further displacement of Tm strands towards actin inner domain apparently uncovering more myosin-binding sites. Thus the number of strongly bound S1 molecules increases at all the stages of the ATPase cycle. These structural changes in the thin filaments may partially be explained by the earlier reported increase in Ca2+-sensitivity caused by the point mutation Arg91Gly that leads to myopathy. The work was supported by the Russian Foundation for Basic Research (No. 11-04-00244a), the RAS Presidium Program (theme No. 7) and the Muscular Dystrophy Campaign
- Добавил в систему: Боровиков Юрий Сергеевич