Looking for Targets to Restore the Contractile Function in Congenital Myopathy Caused by Gln147Pro Tropomyosin
| Autor: | Charles Redwood, Nikita A. Rysev, Olga E. Karpicheva, Yurii S. Borovikov, Armen O. Simonyan |
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| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
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 |
| Zdroj: | International Journal of Molecular Sciences, Vol 21, Iss 7590, p 7590 (2020) International Journal of Molecular Sciences Volume 21 Issue 20 |
| ISSN: | 1661-6596 1422-0067 |
| Popis: | 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+. |
| Databáze: | OpenAIRE |
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