Looking for Targets to Restore the Contractile Function in Congenital Myopathy Caused by Gln147Pro Tropomyosin
| العنوان: | Looking for Targets to Restore the Contractile Function in Congenital Myopathy Caused by Gln147Pro Tropomyosin |
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| المؤلفون: | Charles Redwood, Nikita A. Rysev, Olga E. Karpicheva, Yurii S. Borovikov, Armen O. Simonyan |
| المصدر: | International Journal of Molecular Sciences, Vol 21, Iss 7590, p 7590 (2020) International Journal of Molecular Sciences Volume 21 Issue 20 |
| بيانات النشر: | MDPI AG, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, disease-causing mutations, macromolecular substances, Catalysis, Inorganic Chemistry, lcsh:Chemistry, 03 medical and health sciences, Myosin head, muscle contraction, 0302 clinical medicine, ATP hydrolysis, Myosin, congenital myopathy, medicine, Physical and Theoretical Chemistry, Molecular Biology, lcsh:QH301-705.5, Spectroscopy, Actin, biology, Chemistry, Organic Chemistry, General Medicine, Microfluorimetry, musculoskeletal system, Troponin, Tropomyosin, spatial rearrangements, Computer Science Applications, 030104 developmental biology, lcsh:Biology (General), lcsh:QD1-999, tropomyosin-troponin regulation, biology.protein, Biophysics, medicine.symptom, 030217 neurology & neurosurgery, Muscle contraction |
| الوصف: | We have used the technique of polarized microfluorimetry to obtain new insight into the pathogenesis of skeletal muscle disease caused by the Gln147Pro substitution in &beta tropomyosin (Tpm2.2). The spatial rearrangements of actin, myosin and tropomyosin in the single muscle fiber containing reconstituted thin filaments were studied during simulation of several stages of ATP hydrolysis cycle. The angular orientation of the fluorescence probes bound to tropomyosin was found to be changed by the substitution and was characteristic for a shift of tropomyosin strands closer to the inner actin domains. It was observed both in the absence and in the presence of troponin, Ca2+ and myosin heads at all simulated stages of the ATPase cycle. The mutant showed higher flexibility. Moreover, the Gln147Pro substitution disrupted the myosin-induced displacement of tropomyosin over actin. The irregular positioning of the mutant tropomyosin caused premature activation of actin monomers and a tendency to increase the number of myosin cross-bridges in a state of strong binding with actin at low Ca2+. |
| وصف الملف: | application/pdf |
| اللغة: | English |
| تدمد: | 1661-6596 1422-0067 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8cd6b7738d8a7ec5b6c6e13144c872a6 https://www.mdpi.com/1422-0067/21/20/7590 |
| Rights: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....8cd6b7738d8a7ec5b6c6e13144c872a6 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 16616596 14220067 |
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