1. Structural Biology and Molecular Biophysics

High-resolution structures of the actomyosin-V complex in three nucleotide states provide insights into the force generation mechanism

  1. Sabrina Pospich
  2. H Lee Sweeney
  3. Anne Houdusse
  4. Stefan Raunser  Is a corresponding author
  1. Max Planck Institute of Molecular Physiology, Germany
  2. University of Florida, United States
  3. Institut Curie, Centre National de la Recherche Scientifique, France
https://doi.org/10.7554/eLife.73724
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  1. Sabrina Pospich
  2. H Lee Sweeney
  3. Anne Houdusse
  4. Stefan Raunser
(2021)
High-resolution structures of the actomyosin-V complex in three nucleotide states provide insights into the force generation mechanism
eLife 10:e73724.
https://doi.org/10.7554/eLife.73724
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Abstract

The molecular motor myosin undergoes a series of major structural transitions during its force-producing motor cycle. The underlying mechanism and its coupling to ATP hydrolysis and actin binding is only partially understood, mostly due to sparse structural data on actin-bound states of myosin. Here, we report 26 high-resolution cryo-EM structures of the actomyosin-V complex in the strong-ADP, rigor, and a previously unseen post-rigor transition state that binds the ATP analog AppNHp. The structures reveal a high flexibility of myosin in each state and provide valuable insights into the structural transitions of myosin-V upon ADP release and binding of AppNHp, as well as the actomyosin interface. In addition, they show how myosin is able to specifically alter the structure of F-actin.

Data availability

The atomic models and cryo-EM maps are available in the PDB (Burley et al., 2018) and EMDB databases (Lawson et al., 2011), under following accession numbers: aged PHD-stabilized actomyosin-V in the strong-ADP state: 7PM5, EMD-13521 (central 1er), 7PM6, EMD-13522 (central 3er/2er), 7PM7, EMD-13523 (class 2), 7PM8, EMD-13524 (class 3), 7PM9, EMD-13525 (class 4), 7PMA, EMD-13526 (class 5), 7PMB, EMD-13527 (class 6), 7PMC, EMD-13528 (class 7) ; aged PHD-stabilized actomyosin-V in the rigor state: 7PLT, EMD-13501 (central 1er), 7PLU, EMD-13502 (central 3er/2er), 7PLV, EMD-13503 (class 1), 7PLW, EMD-13504 (class 3) and 7PLX, EMD-13505 (class 4); aged PHD-stabilized actomyosin-V in the PRT state: 7PMD, EMD-13529 (central 1er), 7PME, EMD-13530 (central 3er/2er), 7PMF, EMD-13531 (class 1), 7PMG, EMD-13532 (class 3), 7PMH, EMD-13533 (class 4), 7PMI, EMD-13535 (class 5), 7PMJ, EMD-13536 (class 6), 7PML, EMD-13538 (class 8); young JASP-stabilized actomyosin-V in the rigor state: 7PLY, EMD-13506 (central 1er), 7PLZ, EMD-13507 (central 3er/2er), 7PM0, EMD-13508 (class 1), 7PM1, EMD-13509 (class 2), 7PM2, EMD-13510 (class 4); and young JASP-stabilized F-actin: 7PM3, EMD-13511. The datasets generated during the current study are available from the corresponding author upon reasonable request.

The following data sets were generated

Article and author information

Author details

  1. Sabrina Pospich

    Department of Structural Biochemistry, Max Planck Institute of Molecular Physiology, Dortmund, Germany
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-5119-3039

  2. H Lee Sweeney

    Department of Pharmacology and Therapeutics and the Myology Institute, University of Florida, Gainesville, United States
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6290-8853

  3. Anne Houdusse

    Structural Motility, Institut Curie, Centre National de la Recherche Scientifique, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-8566-0336

  4. Stefan Raunser

    Department of Structural Biochemistry, Max Planck Institute of Molecular Physiology, Dortmund, Germany
    For correspondence
    stefan.raunser@mpi-dortmund.mpg.de
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9373-3016

Funding

Max-Planck-Gesellschaft

  • Stefan Raunser

European Commission (ERC-2019-SyG,856118)

  • Stefan Raunser

Agence Nationale de la Recherche (ANR-17-CE11-0029-01)

  • Anne Houdusse

National Institutes of Health (R01-DC009100)

  • H Lee Sweeney

Centre National de la Recherche Scientifique

  • Anne Houdusse

Studienstiftung des Deutschen Volkes

  • Sabrina Pospich

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Samara L Reck-Peterson, University of California, San Diego, United States

Version history

  1. Preprint posted: September 7, 2021 (view preprint)
  2. Received: September 8, 2021
  3. Accepted: November 22, 2021
  4. Accepted Manuscript published: November 23, 2021 (version 1)
  5. Version of Record published: January 5, 2022 (version 2)

Copyright

© 2021, Pospich et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Sabrina Pospich
  2. H Lee Sweeney
  3. Anne Houdusse
  4. Stefan Raunser
(2021)
High-resolution structures of the actomyosin-V complex in three nucleotide states provide insights into the force generation mechanism
eLife 10:e73724.
https://doi.org/10.7554/eLife.73724

Share this article

https://doi.org/10.7554/eLife.73724

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