Effects of myopathy-causing mutations R91P and R245G in the TPM3 gene on structural and functional properties of slow skeletal muscle tropomyosin
| Autor: | Valentina Y. Berg, Alexander M. Matyushenko, Anastasia M. Kochurova, Dmitrii I. Levitsky, Sergey Yu. Kleymenov, Anastasiia D. Gonchar, Andrey K. Tsaturyan, Galina V. Kopylova, Natalia A. Koubasova, D. V. Shchepkin |
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| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Weakness Generalized muscle weakness Biophysics Tropomyosin Molecular Dynamics Simulation Biochemistry 03 medical and health sciences 0302 clinical medicine medicine Humans Point Mutation Muscle Skeletal Myopathy Molecular Biology Viscosity Chemistry Point mutation Skeletal muscle Cell Biology Actins Troponin Hypotonia Cell biology 030104 developmental biology medicine.anatomical_structure 030220 oncology & carcinogenesis Protein Multimerization medicine.symptom Myopathies Structural Congenital Muscle contraction |
| Zdroj: | Biochemical and Biophysical Research Communications. 534:8-13 |
| ISSN: | 0006-291X |
| DOI: | 10.1016/j.bbrc.2020.11.103 |
| Popis: | Tropomyosin (Tpm) is an actin-binding protein that plays a crucial role in the regulation of muscle contraction. Numerous point mutations in the TPM3 gene encoding Tpm of slow skeletal muscles (Tpm 3.12 or γ-Tpm) are associated with the genesis of various congenital myopathies. Two of these mutations, R91P and R245G, are associated with congenital fiber-type disproportion (CFTD) characterized by hypotonia and generalized muscle weakness. We applied various methods to investigate how these mutations affect the structural and functional properties of γγ-Tpm homodimers. The results show that both these mutations lead to strong structural changes in the γγ-Tpm molecule and significantly impaired its functional properties. These changes in the Tpm properties caused by R91P and R245G mutations give insight into the molecular mechanism of the CFTD development and the weakness of slow skeletal muscles observed in this inherited disease. |
| Databáze: | OpenAIRE |
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