ArticleThe Journal of general physiology2022
Cardiac myosin filaments are directly regulated by calcium.
Article in The Journal of general physiology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 46 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
- The E525K β-Myosin Mutation Causes Hypocontractility in Cardiomyocytes Without Altering Loaded Crossbridge Cycling.bioRxiv : the preprint server for biology · 2026Article
- Assaying the myosin super-relaxed state across muscle types, cells and proteins for understanding muscle biology and use in drug discovery.Nature protocols · 2026Review
- Porcine Left Atrial and Ventricular Thick Filaments Exhibit Distinct Resting Structures and Calcium-dependent Responses.bioRxiv : the preprint server for biology · 2026Article
- 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
- Direct measurement of mavacamten and deoxyATP perturbation of the SRX/DRX ratio in porcine cardiac myofibrils using a simple, accessible and multiplexed approach.Journal of muscle research and cell motility · 2025Article
- Annotating the x-ray diffraction pattern of vertebrate striated muscle.Biophysical journal · 2025Article
- Spatially resolving how cMyBP-C phosphorylation and haploinsufficiency in porcine and human myofibrils affect β-cardiac myosin activity.The Journal of general physiology · 2025Article
- Thick-Filament-Based Regulation and the Determinants of Force Generation.Biomedicines · 2025Article
- Functional control of myosin motors in the cardiac cycle.Nature reviews. Cardiology · 2025Review
- An integrated picture of the structural pathways controlling the heart performance.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Load-dependence of the activation of myosin filaments in heart muscle.The Journal of physiology · 2024Article
- Calcium has a direct effect on thick filament activation in porcine myocardium.The Journal of general physiology · 2024Article
- Differences in thick filament activation in fast rodent skeletal muscle and slow porcine cardiac muscle.The Journal of physiology · 2024Article
- Fast myosin binding protein C knockout in skeletal muscle alters length-dependent activation and myofilament structure.Communications biology · 2024Article
- A Laing distal myopathy-associated proline substitution in the β-myosin rod perturbs myosin cross-bridging activity.The Journal of clinical investigation · 2024Article
- Myosin in autoinhibitedProceedings of the National Academy of Sciences of the United States of America · 2024Article
- The structural OFF and ON states of myosin can be decoupled from the biochemical super- and disordered-relaxed states.PNAS nexus · 2024Article
- The biochemically defined super relaxed state of myosin-A paradox.The Journal of biological chemistry · 2024Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Classically, striated muscle contraction is initiated by calcium (Ca2+)-dependent structural changes in regulatory proteins on actin-containing thin filaments, which allow the binding of myosin motors to generate force. Additionally, dynamic switching between resting off and active on myosin states has been shown to regulate muscle contractility, a recently validated mechanism by novel myosin-targeted therapeutics. The molecular nature of this switching, however, is not understood. Here, using a combination of small-angle x-ray fiber diffraction and biochemical assays with reconstituted systems, we show that cardiac thick filaments are directly Ca2+-regulated. We find that Ca2+ induces a structural transition of myosin heads from ordered off states close to the thick filament to disordered on states closer to the thin filaments. Biochemical assays show a Ca2+-induced transition from an inactive super-relaxed (SRX) state(s) to an active disordered-relaxed (DRX) state(s) in synthetic thick filaments. We show that these transitions are an intrinsic property of cardiac myosin only when assembled into thick filaments and provide a fresh perspective on nature's two orthogonal mechanisms to regulate muscle contraction through the thin and the thick filaments.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.