ArticleJournal of muscle research and cell motility2000
R403Q and L908V mutant beta-cardiac myosin from patients with familial hypertrophic cardiomyopathy exhibit enhanced mechanical performance at the single molecule level.
Article in Journal of muscle research and cell motility, 2000. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
71 citing papers in PubMed, 2 syntheses or guidelines pooled it, 131 citations in OpenAlex.
- Phenotypic Spectrum of Subclinical Sarcomere-Related Hypertrophic Cardiomyopathy and Transition to Overt Disease.Circulation. Genomic and precision medicine · 2024Pooled it
- Comparative analysis of functional assay evidence use by ClinGen Variant Curation Expert Panels.Genome medicine · 2019Pooled it
- Molecular mechanisms of altered contraction with the β-myosin R403Q mutation in porcine ventricular muscle and a human stem cell-derived cardiomyocyte model.Journal of molecular and cellular cardiology · 2025Article
- Modeling thick filament activation suggests a molecular basis for force depression.Biophysical journal · 2024Article
- Molecular Pathways and Animal Models of Cardiomyopathies.Advances in experimental medicine and biology · 2024Article
- Critical Evaluation of Current Hypotheses for the Pathogenesis of Hypertrophic Cardiomyopathy.International journal of molecular sciences · 2022Review
- Hypertrophic cardiomyopathy: Mutations to mechanisms to therapies.Frontiers in physiology · 2022Review
- Alpha and beta myosin isoforms and human atrial and ventricular contraction.Cellular and molecular life sciences : CMLS · 2021Review
- Cardiac myosin contraction and mechanotransduction in health and disease.The Journal of biological chemistry · 2021Review
- Cardiomyocyte Dysfunction in Inherited Cardiomyopathies.International journal of molecular sciences · 2021Review
- The relation between sarcomere energetics and the rate of isometric tension relaxation in healthy and diseased cardiac muscle.Journal of muscle research and cell motility · 2021Article
- Complexity in genetic cardiomyopathies and new approaches for mechanism-based precision medicine.The Journal of general physiology · 2021Article
- Mutations in MYLPF Cause a Novel Segmental Amyoplasia that Manifests as Distal Arthrogryposis.American journal of human genetics · 2020Article
- Disrupted mechanobiology links the molecular and cellular phenotypes in familial dilated cardiomyopathy.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- β-Cardiac myosin hypertrophic cardiomyopathy mutations release sequestered heads and increase enzymatic activity.Nature communications · 2019Article
- The R249Q hypertrophic cardiomyopathy myosin mutation decreases contractility in Drosophila by impeding force production.The Journal of physiology · 2019Article
- The homozygous K280N troponin T mutation alters cross-bridge kinetics and energetics in human HCM.The Journal of general physiology · 2019Article
- Hypertrophic cardiomyopathy R403Q mutation in rabbit β-myosin reduces contractile function at the molecular and myofibrillar levels.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Impact of the Myosin Modulator Mavacamten on Force Generation and Cross-Bridge Behavior in a Murine Model of Hypercontractility.Journal of the American Heart Association · 2018Article
- The Molecular Mechanisms of Mutations in Actin and Myosin that Cause Inherited Myopathy.International journal of molecular sciences · 2018Review
11 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Familial hypertrophic cardiomyopathy (FHC) is a disease of the sarcomere. In the beta-myosin heavy chain gene, which codes for the mechanical enzyme myosin, greater than 40 point mutations have been found that are causal for this disease. We have studied the effect of two mutations, the R403Q and L908V, on myosin molecular mechanics. In the in vitro motility assay, the mutant myosins produced a 30% greater velocity of actin filament movement (v(actin)). At the single molecule level, v(actin) approximately d/t(on), where d is the myosin unitary step displacement and t(on) is the step duration. Laser trap studies were performed at 10 microM MgATP to estimate d and t(on) for the normal and mutant myosin molecules. The increase in v(actin) can be explained by a significant decrease in the average t(on)'s in both the R403Q and L908V mutants (approximately 30 ms) compared to controls (approximately 40 ms), while d was not different for all myosins tested (approximately 7 nm). Thus the mutations affect the kinetics of the cross-bridge cycle without any effect on myosin's inherent motion and force generating capacity. Based on these studies, the primary signal for the hypertrophic response appears to be an apparent gain in function of the individual mutant myosin molecules.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.