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Cardiac and skeletal actin substrates uniquely tune cardiac myosin strain-dependent mechanics
Cardiac ventricular myosin (βmys) translates actin by transducing ATP free energy into mechanical work during muscle contraction. Unitary βmys translation of actin is the step-size. In vitro and in vivo βmys regulates contractile force and velocity autonomously by remixing three different step-sizes...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The Royal Society
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6282072/ https://www.ncbi.nlm.nih.gov/pubmed/30463911 http://dx.doi.org/10.1098/rsob.180143 |
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author | Wang, Yihua Ajtai, Katalin Burghardt, Thomas P. |
author_facet | Wang, Yihua Ajtai, Katalin Burghardt, Thomas P. |
author_sort | Wang, Yihua |
collection | PubMed |
description | Cardiac ventricular myosin (βmys) translates actin by transducing ATP free energy into mechanical work during muscle contraction. Unitary βmys translation of actin is the step-size. In vitro and in vivo βmys regulates contractile force and velocity autonomously by remixing three different step-sizes with adaptive stepping frequencies. Cardiac and skeletal actin isoforms have a specific 1 : 4 stoichiometry in normal adult human ventriculum. Human adults with inheritable hypertrophic cardiomyopathy (HCM) upregulate skeletal actin in ventriculum probably compensating the diseased muscle's inability to meet demand by adjusting βmys force–velocity characteristics. βmys force–velocity characteristics were compared for skeletal versus cardiac actin substrates using ensemble in vitro motility and single myosin assays. Two competing myosin strain-sensitive mechanisms regulate step-size choices dividing single βmys mechanics into low- and high-force regimes. The actin isoforms alter myosin strain-sensitive regulation such that onset of the high-force regime, where a short step-size is a large or major contributor, is offset to higher loads probably by the unique cardiac essential light chain (ELC) N-terminus/cardiac actin contact at Glu6/Ser358. It modifies βmys force–velocity by stabilizing the ELC N-terminus/cardiac actin association. Uneven onset of the high-force regime for skeletal versus cardiac actin modulates force–velocity characteristics as skeletal/cardiac actin fractional content increases in diseased muscle. |
format | Online Article Text |
id | pubmed-6282072 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | The Royal Society |
record_format | MEDLINE/PubMed |
spelling | pubmed-62820722018-12-11 Cardiac and skeletal actin substrates uniquely tune cardiac myosin strain-dependent mechanics Wang, Yihua Ajtai, Katalin Burghardt, Thomas P. Open Biol Research Cardiac ventricular myosin (βmys) translates actin by transducing ATP free energy into mechanical work during muscle contraction. Unitary βmys translation of actin is the step-size. In vitro and in vivo βmys regulates contractile force and velocity autonomously by remixing three different step-sizes with adaptive stepping frequencies. Cardiac and skeletal actin isoforms have a specific 1 : 4 stoichiometry in normal adult human ventriculum. Human adults with inheritable hypertrophic cardiomyopathy (HCM) upregulate skeletal actin in ventriculum probably compensating the diseased muscle's inability to meet demand by adjusting βmys force–velocity characteristics. βmys force–velocity characteristics were compared for skeletal versus cardiac actin substrates using ensemble in vitro motility and single myosin assays. Two competing myosin strain-sensitive mechanisms regulate step-size choices dividing single βmys mechanics into low- and high-force regimes. The actin isoforms alter myosin strain-sensitive regulation such that onset of the high-force regime, where a short step-size is a large or major contributor, is offset to higher loads probably by the unique cardiac essential light chain (ELC) N-terminus/cardiac actin contact at Glu6/Ser358. It modifies βmys force–velocity by stabilizing the ELC N-terminus/cardiac actin association. Uneven onset of the high-force regime for skeletal versus cardiac actin modulates force–velocity characteristics as skeletal/cardiac actin fractional content increases in diseased muscle. The Royal Society 2018-11-21 /pmc/articles/PMC6282072/ /pubmed/30463911 http://dx.doi.org/10.1098/rsob.180143 Text en © 2018 The Authors. http://creativecommons.org/licenses/by/4.0/ Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, provided the original author and source are credited. |
spellingShingle | Research Wang, Yihua Ajtai, Katalin Burghardt, Thomas P. Cardiac and skeletal actin substrates uniquely tune cardiac myosin strain-dependent mechanics |
title | Cardiac and skeletal actin substrates uniquely tune cardiac myosin strain-dependent mechanics |
title_full | Cardiac and skeletal actin substrates uniquely tune cardiac myosin strain-dependent mechanics |
title_fullStr | Cardiac and skeletal actin substrates uniquely tune cardiac myosin strain-dependent mechanics |
title_full_unstemmed | Cardiac and skeletal actin substrates uniquely tune cardiac myosin strain-dependent mechanics |
title_short | Cardiac and skeletal actin substrates uniquely tune cardiac myosin strain-dependent mechanics |
title_sort | cardiac and skeletal actin substrates uniquely tune cardiac myosin strain-dependent mechanics |
topic | Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6282072/ https://www.ncbi.nlm.nih.gov/pubmed/30463911 http://dx.doi.org/10.1098/rsob.180143 |
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