Cell and Tissue BiologyCell and Tissue BiologyЦитология0041-37713034-6061The Russian Academy of Sciences67746810.31857/S0041377124050058DUSZTJArticlesСтатьиResearch ArticleGreen tea catechin EGCG is able to partially restore the regulation of muscle contraction by the troponin-tropomyosin complex, impaired by the Glu150Ala substitution in γ-tropomyosinКатехин зеленого чая EGCG способен частично восстанавливать регуляцию мышечного сокращения тропонин-тропомиозиновым комплексом, нарушенную заменой Glu150Ala в гамма-тропомиозинеTishkovaM. V.TишковаМ. В.
Russian Federation
mariiatiskova@gmail.comKarpichevaO. E.КарпичеваО. Е.
Russian Federation
mariiatiskova@gmail.comBorovikovYu. S.БоровиковЮ. С.
Russian Federation
mariiatiskova@gmail.comAvrovaS. V.АвроваС. В.
Russian Federation
mariiatiskova@gmail.comInstitute of Cytology of the Russian Academy of SciencesИнститут цитологии РАНBoston UniversityБостонский университет15112024665-645046120032025Copyright ©; 2024, Russian Academy of SciencesCopyright ©; 2024, Российская академия наук2024Russian Academy of SciencesРоссийская академия наукhttps://vietnamjournal.ru/0041-3771/article/view/677468

A number of point mutations has been identified in the genes of contractile and regulatory proteins of skeletal muscle that can lead to dysfunction of muscle tissue. The molecular mechanisms of muscle contraction in the presence of mutant muscle proteins in the sarcomere remain poorly understood. In the current study, we examined the impact of the glutamate-to-alanine substitution at position 150 (Glu150Ala) of γ-tropomyosin associated with cap disease and fiber-type disproportion in humans on the molecular mechanisms of troponin-tropomyosin-related regulation of muscle contraction in a single muscle fiber. It is believed that tropomyosin residue Glu150 is not directly involved in the interaction of tropomyosin with actin and myosin interactions; however, according to structural models of thin filaments under low Ca2+ conditions, this residue is located close to site of binding with the C-terminal domain of troponin I. To assess the performance of myosin heads in the presence of Glu150Ala mutant tropomyosin, we measured the polarized fluorescence of 1,5-IAEDANS probe bound to the SH1-helix of myosin. The obtained results indicate an abnormal increase in the number of myosin heads strongly bound to actin during relaxation of muscle fibres containing Glu150Ala mutant tropomyosin. It has been shown that the green tea catechin epigallocatechin gallate (EGCG), known as a modulator of troponin function, inhibits the premature transition of myosin heads into a state of strong actin binding, and thus weakens the damaging effect of the mutation. However, EGCG does not completely restore the effective behavior of myosin cross-bridges during the ATPase cycle.

Идентифицировано множество точечных мутаций в генах сократительных и регуляторных белков скелетных мышц, способных приводить к дисфункции мышечной ткани. Молекулярные механизмы мышечного сокращения в присутствии мутантных мышечных белков в саркомере остаются малоизученными. В представленной работе было исследовано влияние аминокислотной замены остатка глутамата на остаток аланина в позиции 150 (Glu150Ala) γ-тропомиозина, ассоциированной с кэп-миопатией и диспропорцией мышечных волокон человека, на молекулярные механизмы регуляции мышечного сокращения тропонин-тропомиозиновым комплексом в одиночном мышечном волокне. Считается, что остаток Glu150 тропомиозина не принимает непосредственного участия во взаимодействии тропомиозина с актином и миозином; однако, согласно структурным моделям тонких филаментов в условиях низкого уровня Са2+, этот остаток расположен вблизи участка связывания с С-концевым доменом тропонина I. Для оценки работы миозиновых головок в присутствии Glu150Ala-мутантного тропомиозина мы измерили поляризованную флуоресценцию зонда 1,5-IAEDANS, связанного с SH1-спиралью головки миозина. Полученные данные показали аномальное увеличение числа сильно связанных с актином головок миозина при расслаблении мышечного волокна, содержащего Glu150Ala-мутантный тропомиозин. Оказалось, что катехин зеленого чая EGCG, известный как модулятор функции тропонина, ингибирует преждевременный переход миозиновых головок в сильную форму связывания и таким способом ослабляет повреждающее влияние замены GluAla в γ-тропомиозине. Однако EGCG полностью не восстанавливает эффективное прохождение АТФазного цикла миозиновыми поперечными мостиками.

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