Looking for Targets to Restore the Contractile Function in Congenital Myopathy Caused by Gln
| Autor: | Olga E, Karpicheva, Armen O, Simonyan, Nikita A, Rysev, Charles S, Redwood, Yurii S, Borovikov |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
Myotonia Congenita
disease-causing mutations macromolecular substances Tropomyosin Molecular Dynamics Simulation Myosins musculoskeletal system Actins Troponin Article spatial rearrangements muscle contraction Adenosine Triphosphate Amino Acid Substitution Protein Domains congenital myopathy tropomyosin-troponin regulation Animals Humans Calcium Rabbits Cells Cultured |
| Zdroj: | International Journal of Molecular Sciences |
| ISSN: | 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 β-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 |
| Externí odkaz: |
|