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Article

Looking for Targets to Restore the Contractile Function in Congenital Myopathy Caused by Gln147Pro Tropomyosin

1
Institute of Cytology, Russian Academy of Sciences, 4 Tikhoretsky Av., 194064 St. Petersburg, Russia
2
Department of Biophysics, Faculty of Biology, Saint Petersburg State University, 7/9 Universitetskaya Emb., 199034 St. Petersburg, Russia
3
Radcliffe Department of Medicine, University of Oxford, John Radcliffe Hospital, Oxford OX3 9DU, UK
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(20), 7590; https://doi.org/10.3390/ijms21207590
Received: 27 August 2020 / Revised: 6 October 2020 / Accepted: 11 October 2020 / Published: 14 October 2020
(This article belongs to the Special Issue Genetic Basis and Epidemiology of Myopathies)
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+. View Full-Text
Keywords: congenital myopathy; disease-causing mutations; tropomyosin-troponin regulation; muscle contraction; spatial rearrangements congenital myopathy; disease-causing mutations; tropomyosin-troponin regulation; muscle contraction; spatial rearrangements
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MDPI and ACS Style

Karpicheva, O.E.; Simonyan, A.O.; Rysev, N.A.; Redwood, C.S.; Borovikov, Y.S. Looking for Targets to Restore the Contractile Function in Congenital Myopathy Caused by Gln147Pro Tropomyosin. Int. J. Mol. Sci. 2020, 21, 7590. https://doi.org/10.3390/ijms21207590

AMA Style

Karpicheva OE, Simonyan AO, Rysev NA, Redwood CS, Borovikov YS. Looking for Targets to Restore the Contractile Function in Congenital Myopathy Caused by Gln147Pro Tropomyosin. International Journal of Molecular Sciences. 2020; 21(20):7590. https://doi.org/10.3390/ijms21207590

Chicago/Turabian Style

Karpicheva, Olga E., Armen O. Simonyan, Nikita A. Rysev, Charles S. Redwood, and Yurii S. Borovikov 2020. "Looking for Targets to Restore the Contractile Function in Congenital Myopathy Caused by Gln147Pro Tropomyosin" International Journal of Molecular Sciences 21, no. 20: 7590. https://doi.org/10.3390/ijms21207590

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