Tropomodulin–Tropomyosin Interplay Modulates Interaction Between Cardiac Myosin and Thin Filaments
Tropomodulin (Tmod) is an actin-binding protein that interacts with tropomyosin and the actin filament at the pointed end. The influence of Tmod on the thin filament activation in the myocardium is not clear. We studied the interactions of Tmod1 and Tmod4 with the cardiac tropomyosin isoforms Tpm1.1...
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2025-05-01
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| author | Galina V. Kopylova Anastasia M. Kochurova Evgeniia A. Beldiia Andrey V. Slushchev Victoria V. Nefedova Natalia S. Ryabkova Ivan A. Katrukha Daria S. Yampolskaya Alexander M. Matyushenko Daniil V. Shchepkin |
| author_facet | Galina V. Kopylova Anastasia M. Kochurova Evgeniia A. Beldiia Andrey V. Slushchev Victoria V. Nefedova Natalia S. Ryabkova Ivan A. Katrukha Daria S. Yampolskaya Alexander M. Matyushenko Daniil V. Shchepkin |
| author_sort | Galina V. Kopylova |
| collection | DOAJ |
| description | Tropomodulin (Tmod) is an actin-binding protein that interacts with tropomyosin and the actin filament at the pointed end. The influence of Tmod on the thin filament activation in the myocardium is not clear. We studied the interactions of Tmod1 and Tmod4 with the cardiac tropomyosin isoforms Tpm1.1 and Tpm1.2 using size-exclusion chromatography, a pull-down assay, and cross-linking with glutaraldehyde. We found that Tmod1 and Tmod4 form complexes with both Tpm1.1 and Tpm1.2, indicating durable interactions between these proteins. The effects of both Tmods on the actin–myosin interaction were studied using an in vitro motility assay. Tmod did not affect the sliding velocity of bare F-actin. Tmod1 slightly dose-dependently decreased the sliding velocity of F-actin–Tpm1.1 filaments and had no effect on the velocity of F-actin–Tpm1.2 filaments. With ventricular myosin, Tmod1 reduced the calcium sensitivity of the sliding velocity of thin filaments containing Tpm1.1 but did not affect it with filaments containing Tpm1.2. With atrial myosin, Tmod1 decreased the calcium sensitivity of the sliding velocities of thin filaments containing both Tpm1.1 and Tpm1.2. We can conclude that Tmod takes part in the regulation of actin–myosin interactions in the myocardium through interactions with Tpm. The effect of Tmod on the activation of thin filaments depends on the protein isoforms. |
| format | Article |
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| institution | OA Journals |
| issn | 2218-273X |
| language | English |
| publishDate | 2025-05-01 |
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| series | Biomolecules |
| spelling | doaj-art-5fc364c181c44a1ca3a0237d992632522025-08-20T02:33:38ZengMDPI AGBiomolecules2218-273X2025-05-0115572710.3390/biom15050727Tropomodulin–Tropomyosin Interplay Modulates Interaction Between Cardiac Myosin and Thin FilamentsGalina V. Kopylova0Anastasia M. Kochurova1Evgeniia A. Beldiia2Andrey V. Slushchev3Victoria V. Nefedova4Natalia S. Ryabkova5Ivan A. Katrukha6Daria S. Yampolskaya7Alexander M. Matyushenko8Daniil V. Shchepkin9Institute of Immunology and Physiology of the Russian Academy of Sciences, Yekaterinburg 620049, RussiaInstitute of Immunology and Physiology of the Russian Academy of Sciences, Yekaterinburg 620049, RussiaInstitute of Immunology and Physiology of the Russian Academy of Sciences, Yekaterinburg 620049, RussiaResearch Center of Biotechnology of the Russian Academy of Sciences, Moscow 119071, RussiaResearch Center of Biotechnology of the Russian Academy of Sciences, Moscow 119071, RussiaDepartment of Biochemistry, Faculty of Biology, Lomonosov Moscow State University, Moscow 119991, RussiaDepartment of Biochemistry, Faculty of Biology, Lomonosov Moscow State University, Moscow 119991, RussiaResearch Center of Biotechnology of the Russian Academy of Sciences, Moscow 119071, RussiaResearch Center of Biotechnology of the Russian Academy of Sciences, Moscow 119071, RussiaInstitute of Immunology and Physiology of the Russian Academy of Sciences, Yekaterinburg 620049, RussiaTropomodulin (Tmod) is an actin-binding protein that interacts with tropomyosin and the actin filament at the pointed end. The influence of Tmod on the thin filament activation in the myocardium is not clear. We studied the interactions of Tmod1 and Tmod4 with the cardiac tropomyosin isoforms Tpm1.1 and Tpm1.2 using size-exclusion chromatography, a pull-down assay, and cross-linking with glutaraldehyde. We found that Tmod1 and Tmod4 form complexes with both Tpm1.1 and Tpm1.2, indicating durable interactions between these proteins. The effects of both Tmods on the actin–myosin interaction were studied using an in vitro motility assay. Tmod did not affect the sliding velocity of bare F-actin. Tmod1 slightly dose-dependently decreased the sliding velocity of F-actin–Tpm1.1 filaments and had no effect on the velocity of F-actin–Tpm1.2 filaments. With ventricular myosin, Tmod1 reduced the calcium sensitivity of the sliding velocity of thin filaments containing Tpm1.1 but did not affect it with filaments containing Tpm1.2. With atrial myosin, Tmod1 decreased the calcium sensitivity of the sliding velocities of thin filaments containing both Tpm1.1 and Tpm1.2. We can conclude that Tmod takes part in the regulation of actin–myosin interactions in the myocardium through interactions with Tpm. The effect of Tmod on the activation of thin filaments depends on the protein isoforms.https://www.mdpi.com/2218-273X/15/5/727tropomodulincardiac tropomyosin isoformsactin-associated proteinscardiac myosin isoformsactin–myosin interactioncalcium regulation |
| spellingShingle | Galina V. Kopylova Anastasia M. Kochurova Evgeniia A. Beldiia Andrey V. Slushchev Victoria V. Nefedova Natalia S. Ryabkova Ivan A. Katrukha Daria S. Yampolskaya Alexander M. Matyushenko Daniil V. Shchepkin Tropomodulin–Tropomyosin Interplay Modulates Interaction Between Cardiac Myosin and Thin Filaments Biomolecules tropomodulin cardiac tropomyosin isoforms actin-associated proteins cardiac myosin isoforms actin–myosin interaction calcium regulation |
| title | Tropomodulin–Tropomyosin Interplay Modulates Interaction Between Cardiac Myosin and Thin Filaments |
| title_full | Tropomodulin–Tropomyosin Interplay Modulates Interaction Between Cardiac Myosin and Thin Filaments |
| title_fullStr | Tropomodulin–Tropomyosin Interplay Modulates Interaction Between Cardiac Myosin and Thin Filaments |
| title_full_unstemmed | Tropomodulin–Tropomyosin Interplay Modulates Interaction Between Cardiac Myosin and Thin Filaments |
| title_short | Tropomodulin–Tropomyosin Interplay Modulates Interaction Between Cardiac Myosin and Thin Filaments |
| title_sort | tropomodulin tropomyosin interplay modulates interaction between cardiac myosin and thin filaments |
| topic | tropomodulin cardiac tropomyosin isoforms actin-associated proteins cardiac myosin isoforms actin–myosin interaction calcium regulation |
| url | https://www.mdpi.com/2218-273X/15/5/727 |
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