ArticleScience advances2020
The hypertrophic cardiomyopathy mutations R403Q and R663H increase the number of myosin heads available to interact with actin.
Article in Science advances, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers.
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
67 citing papers in PubMed, 97 citations in OpenAlex.
- Probing relaxed myosin states in hypertrophic cardiomyopathy by second harmonic-generation microscopy.eLife · 2026Article
- Mavacamten shows broad benefit in human and mouse models of MYBPC3-related hypertrophic cardiomyopathy.Nature cardiovascular research · 2026Article
- The hypertrophic cardiomyopathy mutation G768R makes cardiac myosin a high duty ratio motor.bioRxiv : the preprint server for biology · 2026Article
- Mavacamten inhibits myosin activity by stabilizing the myosin interacting-heads motif and stalling motor force generation.Science advances · 2026Article
- Comparing cryo-EM structures of the vertebrate cardiac muscle thick filament.Biophysical reviews · 2026Article
- Genetic loci responsible for atrioventricular block in children.Frontiers in cell and developmental biology · 2026Review
- 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
- Resolving zone-specific regulation of cardiac myosin.The Journal of general physiology · 2025Article
- Empagliflozin enhances metabolic efficiency and improves left ventricular hypertrophy in a hypertrophic cardiomyopathy mouse model.European heart journal · 2025Article
- Unraveling Mutation-Induced Protein Communication Pathways in the Actomyosin Complex: Insights from Comprehensive Metadynamics Simulations.The journal of physical chemistry. B · 2025Article
- Beyond conventional therapy: NOX4 as a promising target in cardiomyopathy.Molecular biology reports · 2025Review
- Thick-Filament-Based Regulation and the Determinants of Force Generation.Biomedicines · 2025Article
- Duality in disease: How two amino acid substitutions at actin residue 312 result in opposing forms of cardiomyopathy.The Journal of biological chemistry · 2024Article
- Biochemical characterization of cardiac α-actin mutations A21V and D26N implicated in hypertrophic cardiomyopathy.Cytoskeleton (Hoboken, N.J.) · 2024Article
- Interacting myosin head dynamics and their modification by 2'-deoxy-ADP.Biophysical journal · 2024Article
- Reassessing the unifying hypothesis for hypercontractility caused by myosin mutations in hypertrophic cardiomyopathy.The EMBO journal · 2024Review
- Aficamten is a small-molecule cardiac myosin inhibitor designed to treat hypertrophic cardiomyopathy.Nature cardiovascular research · 2024Article
- Super-relaxed myosins contribute to respiratory muscle hibernation in mechanically ventilated patients.Science translational medicine · 2024Article
- MYH7 R453C induced cardiac remodelling via activating TGF-β/Smad2/3, ERK1/2 and Nox4/ROS/NF-κB signalling pathways.Open biology · 2024Article
- Fast myosin binding protein C knockout in skeletal muscle alters length-dependent activation and myofilament structure.Communications biology · 2024Article
7 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
7 authors at 2 institutions in 2 countries.
Funding
Abstract
Hypertrophic cardiomyopathy (HCM) mutations in β-cardiac myosin and myosin binding protein-C (MyBP-C) lead to hypercontractility of the heart, an early hallmark of HCM. We show that hypercontractility caused by the HCM-causing mutation R663H cannot be explained by changes in fundamental myosin contractile parameters, much like the HCM-causing mutation R403Q. Using enzymatic assays with purified human β-cardiac myosin, we provide evidence that both mutations cause hypercontractility by increasing the number of functionally accessible myosin heads. We also demonstrate that the myosin mutation R403Q, but not R663H, ablates the binding of myosin with the C0-C7 fragment of MyBP-C. Furthermore, addition of C0-C7 decreases the wild-type myosin basal ATPase single turnover rate, while the mutants do not show a similar reduction. These data suggest that a primary mechanism of action for these mutations is to increase the number of myosin heads functionally available for interaction with actin, which could contribute to hypercontractility.
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.