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Multistep orthophosphate release tunes actomyosin energy transduction

Author

Listed:
  • Luisa Moretto

    (Linnaeus University)

  • Marko Ušaj

    (Linnaeus University)

  • Oleg Matusovsky

    (McGill University)

  • Dilson E. Rassier

    (McGill University)

  • Ran Friedman

    (Linnaeus University)

  • Alf Månsson

    (Linnaeus University)

Abstract

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.

Suggested Citation

  • Luisa Moretto & Marko Ušaj & Oleg Matusovsky & Dilson E. Rassier & Ran Friedman & Alf Månsson, 2022. "Multistep orthophosphate release tunes actomyosin energy transduction," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-32110-9
    DOI: 10.1038/s41467-022-32110-9
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    References listed on IDEAS

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    1. Serena Governali & Marco Caremani & Cristina Gallart & Irene Pertici & Ger Stienen & Gabriella Piazzesi & Coen Ottenheijm & Vincenzo Lombardi & Marco Linari, 2020. "Orthophosphate increases the efficiency of slow muscle-myosin isoform in the presence of omecamtiv mecarbil," Nature Communications, Nature, vol. 11(1), pages 1-12, December.
    2. Vicente J. Planelles-Herrero & James J. Hartman & Julien Robert-Paganin & Fady I. Malik & Anne Houdusse, 2017. "Mechanistic and structural basis for activation of cardiac myosin force production by omecamtiv mecarbil," Nature Communications, Nature, vol. 8(1), pages 1-10, December.
    3. Rani Zananiri & Sivasubramanyan Mangapuram Venkata & Vera Gaydar & Dan Yahalom & Omri Malik & Sergei Rudnizky & Oded Kleifeld & Ariel Kaplan & Arnon Henn, 2022. "Auxiliary ATP binding sites support DNA unwinding by RecBCD," Nature Communications, Nature, vol. 13(1), pages 1-14, December.
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    Cited by:

    1. Christopher Marang & Brent Scott & James Chambers & Laura K. Gunther & Christopher M. Yengo & Edward P. Debold, 2023. "A mutation in switch I alters the load-dependent kinetics of myosin Va," Nature Communications, Nature, vol. 14(1), pages 1-11, December.

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