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Интеллектуальная Система Тематического Исследования НАукометрических данных |
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The effect of the congenital myopathy-causing mutation E139del in TPM2 gene on movement of β-tropomyosin strands and actin-myosin interaction during the ATPase cycleтезисы доклада
- Авторы: Rysev NA, Avrova SV, Karpicheva OE, Piers A., Redwood CS, Borovikov YS
- Сборник: In Abstracts of International Symposium «Biological Motility: New facts and hypotheses», Pushchino, Russia
- Тезисы
- Год издания: 2016
- Первая страница: 202
- Последняя страница: 203
- Аннотация: Tropomyosin (TM) is a two-chained α-helical coiled-coil protein. Its rod-like molecules associate head-to-tail to form continuous strands that run along the entire length of F-actin. Amino acid sequence of the TM molecule reflects the presence of 7 pseudo-repeats (about 40 amino acids each) that has been postulated to relate to the binding sites for the 7 actin monomers along the length of a TM molecule, conforming to the F-actin helix. The position of TM strands in troponin-free actin filaments was found to be correlated with the number of the switched on actin subunits, and the amount of the strongly bound myosin heads during the ATPase cycle. In skeletal muscles there are three main tropomyosin isoforms, α-TM, β-TM and γ -TM, which are encoded by the TPM1, TPM2 and TPM3 genes, respectively. Mutations in the TPM2 gene demonstrate a wide spectrum of clinically, histologically and genetically variable neuromuscular disorders. One of these mutations is E139del. The mutation causes cap disease, characterized by cap-like structures located under the sarcolemma. We have investigated how the E139del mutation in TPM2 gene of β-tropomyosin affects TM’s position on actin filament and the spatial arrangement of actin subunits and myosin heads at different mimicked stages of the ATPase cycle in ghost muscle fibres by polarized fluorimetry. We labelled recombinant wild-type and mutant E139del TMs with 5-IAF, F-actin with FITC-phalloidin and myosin S1 with 1.5-IAEDANS and incorporated them into ghost muscle fibres. The reconstructed actin filaments of the fibres were decorated by myosin S1 and polarized fluorescence was measured at different stages of the ATPase cycle. It was found that at transition from the weak-binding to the strong-binding actomyosin states actin monomers turned to the filament periphery and the TM strands moved towards the inner domains of actin subunits. The E139del mutation kept the TM strands near the inner domains of actin but decreased the number of the switched on actin monomers throughout the cycle. This mutation inhibits the amount of strongly bound myosin heads throughout the ATPase cycle. The aberrant movement of the E139del TM causes abnormal response of the contractile system that may result in muscle weakness observed in patients with the E139del mutation. This work was supported by the Russian Foundation for Basic Research (grants №16-34-00865mol and № 14-04-00454).
- Добавил в систему: Карпичева Ольга Евгеньевна