High-resolution structures of the actomyosin-V complex in three nucleotide states provide insights into the force generation mechanism
- Max Planck Institute of Molecular Physiology, Germany
- University of Florida, United States
- Institut Curie, Centre National de la Recherche Scientifique, France
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.
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Cryo-EM structure of the actomyosin-V complex in the strong-ADP state (central 1er)RCSB Protein Data Bank, 7PM5.
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Cryo-EM structure of the actomyosin-V complex in the strong-ADP state (central 3er/2er)RCSB Protein Data Bank, 7PM6.
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Cryo-EM structure of the actomyosin-V complex in the rigor state (central 1er)RCSB Protein Data Bank, 7PLT.
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Cryo-EM structure of the actomyosin-V complex in the rigor state (central 3er/2er)RCSB Protein Data Bank, 7PLU.
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Cryo-EM structure of the actomyosin-V complex in the rigor state (central 1er, class 1)RCSB Protein Data Bank, 7PLV.
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Cryo-EM structure of the actomyosin-V complex in the rigor state (central 1er, class 2)RCSB Protein Data Bank, 7PLW.
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Cryo-EM structure of the actomyosin-V complex in the rigor state (central 1er, class 4)RCSB Protein Data Bank, 7PLX.
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Cryo-EM structure of young JASP-stabilized F-actin (central 3er)RCSB Protein Data Bank, 7PM3.
Article and author information
Author details
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
- Samara L Reck-Peterson, University of California, San Diego, United States
Version history
- Preprint posted: September 7, 2021 (view preprint)
- Received: September 8, 2021
- Accepted: November 22, 2021
- Accepted Manuscript published: November 23, 2021 (version 1)
- 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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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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