ArticleNature communications2019
β-Cardiac myosin hypertrophic cardiomyopathy mutations release sequestered heads and increase enzymatic activity.
Article in Nature communications, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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Who cites it
59 citing papers in PubMed, 87 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
- Beta-Adrenergic Stimulation andbioRxiv : the preprint server for biology · 2026Article
- Cryo-EM reveals how cardiomyopathy therapeutic drugs modulate the myosin motors of the heart.Science advances · 2026Article
- Early Cytoskeletal Remodeling Drives Hypertrophic Cardiomyopathy Pathogenesis inJournal of cardiovascular development and disease · 2025Article
- Loss or Gain: Myosin Heavy Chain Truncations in Hypertrophic Cardiomyopathy.Journal of the American Heart Association · 2025Article
- Cryo-EM Reveals How Cardiomyopathy Therapeutic Drugs Modulate the Myosin Motors of the Heart.bioRxiv : the preprint server for biology · 2025Article
- Imaging of metabolic dysfunction in genetic cardiomyopathies.The international journal of cardiovascular imaging · 2025Review
- Understanding hypertrophic cardiomyopathy and its regulation by myosin drugs.Protein science : a publication of the Protein Society · 2025Article
- A FRET assay to monitor different structural states of human β-cardiac myosin including the interacting-heads motif.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Relationship between genotype and clinical phenotype of hypertrophic cardiomyopathy.World journal of cardiology · 2025Review
- Dynamics of β-cardiac myosin between the super-relaxed and disordered-relaxed states.The Journal of biological chemistry · 2025Article
- A FRET assay to quantitate levels of the human β-cardiac myosin interacting heads motif based on its near-atomic resolution structure.bioRxiv : the preprint server for biology · 2024Article
- Biochemical characterization of cardiac α-actin mutations A21V and D26N implicated in hypertrophic cardiomyopathy.Cytoskeleton (Hoboken, N.J.) · 2024Article
- Myocardial contractility characteristics of hypertrophic cardiomyopathy patients with and without sarcomere mutation.Heart and vessels · 2024Article
- Exploring Protein Conformational Changes Using a Large-Scale Biophysical Sampling Augmented Deep Learning Strategy.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 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
- UNC-45 assisted myosin folding depends on a conserved FXNature communications · 2024Article
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Hypertrophic cardiomyopathy (HCM) affects 1 in 500 people and leads to hyper-contractility of the heart. Nearly 40 percent of HCM-causing mutations are found in human β-cardiac myosin. Previous studies looking at the effect of HCM mutations on the force, velocity and ATPase activity of the catalytic domain of human β-cardiac myosin have not shown clear trends leading to hypercontractility at the molecular scale. Here we present functional data showing that four separate HCM mutations located at the myosin head-tail (R249Q, H251N) and head-head (D382Y, R719W) interfaces of a folded-back sequestered state referred to as the interacting heads motif (IHM) lead to a significant increase in the number of heads functionally accessible for interaction with actin. These results provide evidence that HCM mutations can modulate myosin activity by disrupting intramolecular interactions within the proposed sequestered state, which could lead to hypercontractility at the molecular level.
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