ArticleProceedings of the National Academy of Sciences of the United States of America2023
Structural OFF/ON transitions of myosin in relaxed porcine myocardium predict calcium-activated force.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 58 citations in OpenAlex.
- Diastolic contributors in cardiomyocytes of a cardiometabolic HFpEF-like mouse model.The Journal of general physiology · 2026Article
- Probing relaxed myosin states in hypertrophic cardiomyopathy by second harmonic-generation microscopy.eLife · 2026Article
- Temperature dependence of activation of thick and thin filaments in skeletal and cardiac muscles.Journal of muscle research and cell motility · 2026Review
- Myosin motor dynamics and cardiac function: Insights from in vivo small-angle X-ray scattering and pressure-volume analysis.The Journal of physiology · 2026Article
- Severe obesity in human HFpEF alters contractile protein function and organization.Science (New York, N.Y.) · 2026Article
- Porcine Left Atrial and Ventricular Thick Filaments Exhibit Distinct Resting Structures and Calcium-dependent Responses.bioRxiv : the preprint server for biology · 2026Article
- Titin's P-zone domains A164-167 are essential for thick filament structural arrangement.The Journal of general physiology · 2026Article
- A primer on the methods of skeletal and cardiac muscle mechanics using permeabilized preparations.The Journal of general physiology · 2026Review
- Comparison of Predicted X-Ray Fiber Diffraction Patterns from All-Atom and Coarse-Grained Actin Filament Models Under Nonuniform Strain.International journal of molecular sciences · 2025Article
- Annotating the x-ray diffraction pattern of vertebrate striated muscle.Biophysical journal · 2025Article
- Hypertrophic cardiomyopathy mutations Y115H and E497D disrupt the folded-back state of human β-cardiac myosin allosterically.Nature communications · 2025Article
- A FRET assay to monitor different structural states of human β-cardiac myosin including the interacting-heads motif.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- ATP directly modulates thick filament structure and function in porcine myocardium.Biophysical journal · 2025Article
- Various challenges in understanding the thick filaments, within and outside skeletal and cardiac muscles.Biophysical reviews · 2025Article
- Consecutive SSCs increase the SSC effect in skinned rat muscle fibres.Pflugers Archiv : European journal of physiology · 2025Article
- A combined experimental and computational analysis of mantATP turnover in skinned muscle fibers.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Cellular and molecular contractile function in aged human skeletal muscle is altered by phosphate and acidosis and partially reversed with an ATP analog.American journal of physiology. Cell physiology · 2025Article
- Thick-Filament-Based Regulation and the Determinants of Force Generation.Biomedicines · 2025Article
- A FRET assay to quantitate levels of the human β-cardiac myosin interacting heads motif based on its near-atomic resolution structure.bioRxiv : the preprint server for biology · 2024Article
- Interacting myosin head dynamics and their modification by 2'-deoxy-ADP.Biophysical journal · 2024Article
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Contraction in striated muscle is initiated by calcium binding to troponin complexes, but it is now understood that dynamic transition of myosin between resting, ordered OFF states on thick filaments and active, disordered ON states that can bind to thin filaments is critical in regulating muscle contractility. These structural OFF to ON transitions of myosin are widely assumed to correspond to transitions from the biochemically defined, energy-sparing, super-relaxed (SRX) state to the higher ATPase disordered-relaxed (DRX) state. Here we examined the effect of 2'-deoxy-ATP (dATP), a naturally occurring energy substrate for myosin, on the structural OFF to ON transitions of myosin motors in porcine cardiac muscle thick filaments. Small-angle X-ray diffraction revealed that titrating dATP in relaxation solutions progressively moves the myosin heads from ordered OFF states on the thick filament backbone to disordered ON states closer to thin filaments. Importantly, we found that the structural OFF to ON transitions are not equivalent to the biochemically defined SRX to DRX transitions and that the dATP-induced structural OFF to ON transitions of myosin motors in relaxed muscle are strongly correlated with submaximal force augmentation by dATP. These results indicate that structural OFF to ON transitions of myosin in relaxed muscle can predict the level of force attained in calcium-activated cardiac muscle. Computational modeling and stiffness measurements suggest a final step in the OFF to ON transition may involve a subset of DRX myosins that form weakly bound cross-bridges prior to becoming active force-producing cross-bridges.
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