ArticleProceedings of the National Academy of Sciences of the United States of America2002
Mutation of the myosin converter domain alters cross-bridge elasticity.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed, 89 citations in OpenAlex.
- Multi-omics insight into cardiac myofibril remodeling in post-prandial Burmese pythons.Communications biology · 2026Article
- Hypertrophic cardiomyopathy-linked Tnnc1 variants are associated with distinct myopathic changes in slow skeletal muscle of mice.Journal of muscle research and cell motility · 2026Article
- The hypertrophic cardiomyopathy mutation G768R makes cardiac myosin a high duty ratio motor.bioRxiv : the preprint server for biology · 2026Article
- Multi-omics Insight into Cardiac Myofibril Remodeling in Post-Prandial Burmese Pythons.bioRxiv : the preprint server for biology · 2026Article
- Myosin essential light chain 1sa decelerates actin and thin filament gliding on β-myosin molecules.The Journal of general physiology · 2022Article
- Cardiac ventricular myosin and slow skeletal myosin exhibit dissimilar chemomechanical properties despite bearing the same myosin heavy chain isoform.The Journal of biological chemistry · 2022Article
- Muscle LIM Protein Force-Sensing Mediates Sarcomeric Biomechanical Signaling in Human Familial Hypertrophic Cardiomyopathy.Circulation · 2022Article
- Critical Evaluation of Current Hypotheses for the Pathogenesis of Hypertrophic Cardiomyopathy.International journal of molecular sciences · 2022Review
- Myosin Heavy Chain Converter Domain Mutations Drive Early-Stage Changes in Extracellular Matrix Dynamics in Hypertrophic Cardiomyopathy.Frontiers in cell and developmental biology · 2022Article
- Alpha and beta myosin isoforms and human atrial and ventricular contraction.Cellular and molecular life sciences : CMLS · 2021Review
- Cardiomyopathy mutations impact the actin-activated power stroke of human cardiac myosin.Biophysical journal · 2021Article
- Optomechanical detection of vibration modes of a single bacterium.Nature nanotechnology · 2020Article
- Cycling Cross-Bridges Contribute to Thin Filament Activation in Human Slow-Twitch Fibers.Frontiers in physiology · 2020Article
- Myosin motor domains carrying mutations implicated in early or late onset hypertrophic cardiomyopathy have similar properties.The Journal of biological chemistry · 2019Article
- The load dependence of muscle's force-velocity curve is modulated by alternative myosin converter domains.American journal of physiology. Cell physiology · 2019Article
- The R249Q hypertrophic cardiomyopathy myosin mutation decreases contractility in Drosophila by impeding force production.The Journal of physiology · 2019Article
- Altered force generation and cell-to-cell contractile imbalance in hypertrophic cardiomyopathy.Pflugers Archiv : European journal of physiology · 2019Review
- Converter domain mutations in myosin alter structural kinetics and motor function.The Journal of biological chemistry · 2019Article
- Hypertrophic cardiomyopathy disease results from disparate impairments of cardiac myosin function and auto-inhibition.Nature communications · 2018Article
- Mechanical parameters of the molecular motor myosin II determined in permeabilised fibres from slow and fast skeletal muscles of the rabbit.The Journal of physiology · 2018Article
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Elastic distortion of a structural element of the actomyosin complex is fundamental to the ability of myosin to generate motile forces. An elastic element allows strain to develop within the actomyosin complex (cross-bridge) before movement. Relief of this strain then drives filament sliding, or more generally, movement of a cargo. Even with the known crystal structure of the myosin head, however, the structural element of the actomyosin complex in which elastic distortion occurs remained unclear. To assign functional relevance to various structural elements of the myosin head, e.g., to identify the elastic element within the cross-bridge, we studied mechanical properties of muscle fibers from patients with familial hypertrophic cardiomyopathy with point mutations in the head domain of the beta-myosin heavy chain. We found that the Arg-719 --> Trp (Arg719Trp) mutation, which is located in the converter domain of the myosin head fragment, causes an increase in force generation and fiber stiffness under isometric conditions by 48-59%. Under rigor and relaxing conditions, fiber stiffness was 45-47% higher than in control fibers. Yet, kinetics of active cross-bridge cycling were unchanged. These findings, especially the increase in fiber stiffness under rigor conditions, indicate that cross-bridges with the Arg719Trp mutation are more resistant to elastic distortion. The data presented here strongly suggest that the converter domain that forms the junction between the catalytic and the light-chain-binding domain of the myosin head is not only essential for elastic distortion of the cross-bridge, but that the main elastic distortion may even occur within the converter domain itself.
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