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Ca(2+) attenuates nucleation activity of leiomodin

A transient increase in Ca(2+) concentration in sarcomeres is essential for their proper function. Ca(2+) drives striated muscle contraction via binding to the troponin complex of the thin filament to activate its interaction with the myosin thick filament. In addition to the troponin complex, the m...

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Autores principales: Smith, Garry E., Tolkatchev, Dmitri, Risi, Cristina, Little, Madison, Gregorio, Carol C., Galkin, Vitold E., Kostyukova, Alla S.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley & Sons, Inc. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9207750/
https://www.ncbi.nlm.nih.gov/pubmed/35762710
http://dx.doi.org/10.1002/pro.4358
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author Smith, Garry E.
Tolkatchev, Dmitri
Risi, Cristina
Little, Madison
Gregorio, Carol C.
Galkin, Vitold E.
Kostyukova, Alla S.
author_facet Smith, Garry E.
Tolkatchev, Dmitri
Risi, Cristina
Little, Madison
Gregorio, Carol C.
Galkin, Vitold E.
Kostyukova, Alla S.
author_sort Smith, Garry E.
collection PubMed
description A transient increase in Ca(2+) concentration in sarcomeres is essential for their proper function. Ca(2+) drives striated muscle contraction via binding to the troponin complex of the thin filament to activate its interaction with the myosin thick filament. In addition to the troponin complex, the myosin essential light chain and myosin‐binding protein C were also found to be Ca(2+) sensitive. However, the effects of Ca(2+) on the function of the tropomodulin family proteins involved in regulating thin filament formation have not yet been studied. Leiomodin, a member of the tropomodulin family, is an actin nucleator and thin filament elongator. Using pyrene‐actin polymerization assay and transmission electron microscopy, we show that the actin nucleation activity of leiomodin is attenuated by Ca(2+). Using circular dichroism and nuclear magnetic resonance spectroscopy, we demonstrate that the mostly disordered, negatively charged region of leiomodin located between its first two actin‐binding sites binds Ca(2+). We propose that Ca(2+) binding to leiomodin results in the attenuation of its nucleation activity. Our data provide further evidence regarding the role of Ca(2+) as an ultimate regulator of the ensemble of sarcomeric proteins essential for muscle function. SUMMARY STATEMENT: Ca(2+) fluctuations in striated muscle sarcomeres modulate contractile activity via binding to several distinct families of sarcomeric proteins. The effects of Ca(2+) on the activity of leiomodin—an actin nucleator and thin filament length regulator—have remained unknown. In this study, we demonstrate that Ca(2+) binds directly to leiomodin and attenuates its actin nucleating activity. Our data emphasizes the ultimate role of Ca(2+) in the regulation of the sarcomeric protein interactions.
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spelling pubmed-92077502022-06-27 Ca(2+) attenuates nucleation activity of leiomodin Smith, Garry E. Tolkatchev, Dmitri Risi, Cristina Little, Madison Gregorio, Carol C. Galkin, Vitold E. Kostyukova, Alla S. Protein Sci Full‐length Papers A transient increase in Ca(2+) concentration in sarcomeres is essential for their proper function. Ca(2+) drives striated muscle contraction via binding to the troponin complex of the thin filament to activate its interaction with the myosin thick filament. In addition to the troponin complex, the myosin essential light chain and myosin‐binding protein C were also found to be Ca(2+) sensitive. However, the effects of Ca(2+) on the function of the tropomodulin family proteins involved in regulating thin filament formation have not yet been studied. Leiomodin, a member of the tropomodulin family, is an actin nucleator and thin filament elongator. Using pyrene‐actin polymerization assay and transmission electron microscopy, we show that the actin nucleation activity of leiomodin is attenuated by Ca(2+). Using circular dichroism and nuclear magnetic resonance spectroscopy, we demonstrate that the mostly disordered, negatively charged region of leiomodin located between its first two actin‐binding sites binds Ca(2+). We propose that Ca(2+) binding to leiomodin results in the attenuation of its nucleation activity. Our data provide further evidence regarding the role of Ca(2+) as an ultimate regulator of the ensemble of sarcomeric proteins essential for muscle function. SUMMARY STATEMENT: Ca(2+) fluctuations in striated muscle sarcomeres modulate contractile activity via binding to several distinct families of sarcomeric proteins. The effects of Ca(2+) on the activity of leiomodin—an actin nucleator and thin filament length regulator—have remained unknown. In this study, we demonstrate that Ca(2+) binds directly to leiomodin and attenuates its actin nucleating activity. Our data emphasizes the ultimate role of Ca(2+) in the regulation of the sarcomeric protein interactions. John Wiley & Sons, Inc. 2022-06-20 2022-07 /pmc/articles/PMC9207750/ /pubmed/35762710 http://dx.doi.org/10.1002/pro.4358 Text en © 2022 The Authors. Protein Science published by Wiley Periodicals LLC on behalf of The Protein Society. https://creativecommons.org/licenses/by-nc/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc/4.0/ (https://creativecommons.org/licenses/by-nc/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
spellingShingle Full‐length Papers
Smith, Garry E.
Tolkatchev, Dmitri
Risi, Cristina
Little, Madison
Gregorio, Carol C.
Galkin, Vitold E.
Kostyukova, Alla S.
Ca(2+) attenuates nucleation activity of leiomodin
title Ca(2+) attenuates nucleation activity of leiomodin
title_full Ca(2+) attenuates nucleation activity of leiomodin
title_fullStr Ca(2+) attenuates nucleation activity of leiomodin
title_full_unstemmed Ca(2+) attenuates nucleation activity of leiomodin
title_short Ca(2+) attenuates nucleation activity of leiomodin
title_sort ca(2+) attenuates nucleation activity of leiomodin
topic Full‐length Papers
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9207750/
https://www.ncbi.nlm.nih.gov/pubmed/35762710
http://dx.doi.org/10.1002/pro.4358
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