ArticleProceedings of the National Academy of Sciences of the United States of America2018
Deciphering the super relaxed state of human β-cardiac myosin and the mode of action of mavacamten from myosin molecules to muscle fibers.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 262 papers, 4 of them syntheses that pooled it.
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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.
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Who cites it
262 citing papers in PubMed, 4 syntheses or guidelines pooled it, 396 citations in OpenAlex.
- Efficacy and Safety of Mavacamten and Aficamten in Obstructive and Nonobstructive Hypertrophic Cardiomyopathy: A Systematic Review and Meta-Analysis.Critical pathways in cardiology · 2026Pooled it
- Phenotypic Spectrum of Subclinical Sarcomere-Related Hypertrophic Cardiomyopathy and Transition to Overt Disease.Circulation. Genomic and precision medicine · 2024Pooled it
- Pooled it
- Efficacy and safety of cardiac myosin inhibitors for symptomatic hypertrophic cardiomyopathy: a meta-analysis of randomized controlled trials.Frontiers in cardiovascular medicine · 2024Pooled it
- Effect of Activated Charcoal on Mavacamten Pharmacokinetics in Healthy Participants.American journal of cardiovascular drugs : drugs, devices, and other interventions · 2024Trial
- Long-Term Safety and Efficacy of Mavacamten in Symptomatic Obstructive Hypertrophic Cardiomyopathy: Interim Results of the PIONEER-OLE Study.Journal of the American Heart Association · 2024Trial
- Evidence for a role of adverse sarcomere signaling in atrial fibrillation induction.Journal of molecular and cellular cardiology plus · 2026Review
- Therapeutic upregulation of gene expression in inherited cardiomyopathies from current approaches to future directions.Nature cardiovascular research · 2026Review
- Mechanistic diversity within RLC-dependent myosin ATPase inhibitors differentiates EDG-7500, a diastolic-selective cardiac sarcomere modulator.JCI insight · 2026Article
- Kinetic modeling of mant-ATP turnover to interpret the biochemically defined myosin SRX state.Biophysical journal · 2026Article
- First-Phase Ejection Fraction: A Novel Approach to Detecting Early Systolic Dysfunction in Hypertrophic Cardiomyopathy.Echocardiography (Mount Kisco, N.Y.) · 2026Article
- The structure of the native cardiac crossbridge in the rigor state.Science advances · 2026Article
- Structure-Function Relationship as the Foundation for Cardiac Myosin Inhibition in Hypertrophic Cardiomyopathy.Circulation · 2026Article
- Dynamic LVOT Obstruction After Mitral Valve Repair in HCM: Treatment With a Cardiac Myosin Inhibitor.JACC. Case reports · 2026Article
- Probing relaxed myosin states in hypertrophic cardiomyopathy by second harmonic-generation microscopy.eLife · 2026Article
- Myosin motor dynamics and cardiac function: Insights from in vivo small-angle X-ray scattering and pressure-volume analysis.The Journal of physiology · 2026Article
- Knowledge mapping of targeted therapy for hypertrophic cardiomyopathy: A bibliometric analysis of myosin inhibitor research.Medicine · 2026Article
- Evaluation of the effect of mavacamten on left ventricular function in obstructive hypertrophic cardiomyopathy using myocardial work.Clinical physiology and functional imaging · 2026Article
- Structural basis of nonmuscle myosin-2 autoinhibition mechanisms.Nature communications · 2026Article
- Force-Induced Ankle Opening Reveals Mechanical Stabilization of the Ankle of Human β-Cardiac Myosin.ACS nano · 2026Article
202 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
16 authors at 6 institutions in 1 country.
Funding
Abstract
Mutations in β-cardiac myosin, the predominant motor protein for human heart contraction, can alter power output and cause cardiomyopathy. However, measurements of the intrinsic force, velocity, and ATPase activity of myosin have not provided a consistent mechanism to link mutations to muscle pathology. An alternative model posits that mutations in myosin affect the stability of a sequestered, super relaxed state (SRX) of the protein with very slow ATP hydrolysis and thereby change the number of myosin heads accessible to actin. Here we show that purified human β-cardiac myosin exists partly in an SRX and may in part correspond to a folded-back conformation of myosin heads observed in muscle fibers around the thick filament backbone. Mutations that cause hypertrophic cardiomyopathy destabilize this state, while the small molecule mavacamten promotes it. These findings provide a biochemical and structural link between the genetics and physiology of cardiomyopathy with implications for therapeutic strategies.
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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.