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Multistep orthophosphate release tunes actomyosin energy transduction
Muscle contraction and a range of critical cellular functions rely on force-producing interactions between myosin motors and actin filaments, powered by turnover of adenosine triphosphate (ATP). The relationship between release of the ATP hydrolysis product ortophosphate (Pi) from the myosin active...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9356070/ https://www.ncbi.nlm.nih.gov/pubmed/35931685 http://dx.doi.org/10.1038/s41467-022-32110-9 |
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author | Moretto, Luisa Ušaj, Marko Matusovsky, Oleg Rassier, Dilson E. Friedman, Ran Månsson, Alf |
author_facet | Moretto, Luisa Ušaj, Marko Matusovsky, Oleg Rassier, Dilson E. Friedman, Ran Månsson, Alf |
author_sort | Moretto, Luisa |
collection | PubMed |
description | Muscle contraction and a range of critical cellular functions rely on force-producing interactions between myosin motors and actin filaments, powered by turnover of adenosine triphosphate (ATP). The relationship between release of the ATP hydrolysis product ortophosphate (Pi) from the myosin active site and the force-generating structural change, the power-stroke, remains enigmatic despite its central role in energy transduction. Here, we present a model with multistep Pi-release that unifies current conflicting views while also revealing additional complexities of potential functional importance. The model is based on our evidence from kinetics, molecular modelling and single molecule fluorescence studies of Pi binding outside the active site. It is also consistent with high-speed atomic force microscopy movies of single myosin II molecules without Pi at the active site, showing consecutive snapshots of pre- and post-power stroke conformations. In addition to revealing critical features of energy transduction by actomyosin, the results suggest enzymatic mechanisms of potentially general relevance. |
format | Online Article Text |
id | pubmed-9356070 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-93560702022-08-07 Multistep orthophosphate release tunes actomyosin energy transduction Moretto, Luisa Ušaj, Marko Matusovsky, Oleg Rassier, Dilson E. Friedman, Ran Månsson, Alf Nat Commun Article Muscle contraction and a range of critical cellular functions rely on force-producing interactions between myosin motors and actin filaments, powered by turnover of adenosine triphosphate (ATP). The relationship between release of the ATP hydrolysis product ortophosphate (Pi) from the myosin active site and the force-generating structural change, the power-stroke, remains enigmatic despite its central role in energy transduction. Here, we present a model with multistep Pi-release that unifies current conflicting views while also revealing additional complexities of potential functional importance. The model is based on our evidence from kinetics, molecular modelling and single molecule fluorescence studies of Pi binding outside the active site. It is also consistent with high-speed atomic force microscopy movies of single myosin II molecules without Pi at the active site, showing consecutive snapshots of pre- and post-power stroke conformations. In addition to revealing critical features of energy transduction by actomyosin, the results suggest enzymatic mechanisms of potentially general relevance. Nature Publishing Group UK 2022-08-05 /pmc/articles/PMC9356070/ /pubmed/35931685 http://dx.doi.org/10.1038/s41467-022-32110-9 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Moretto, Luisa Ušaj, Marko Matusovsky, Oleg Rassier, Dilson E. Friedman, Ran Månsson, Alf Multistep orthophosphate release tunes actomyosin energy transduction |
title | Multistep orthophosphate release tunes actomyosin energy transduction |
title_full | Multistep orthophosphate release tunes actomyosin energy transduction |
title_fullStr | Multistep orthophosphate release tunes actomyosin energy transduction |
title_full_unstemmed | Multistep orthophosphate release tunes actomyosin energy transduction |
title_short | Multistep orthophosphate release tunes actomyosin energy transduction |
title_sort | multistep orthophosphate release tunes actomyosin energy transduction |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9356070/ https://www.ncbi.nlm.nih.gov/pubmed/35931685 http://dx.doi.org/10.1038/s41467-022-32110-9 |
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