ArticleNature structural & molecular biology2017
The myosin mesa and the basis of hypercontractility caused by hypertrophic cardiomyopathy mutations.
Article in Nature structural & molecular biology, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 153 papers.
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Who cites it
153 citing papers in PubMed, 226 citations in OpenAlex.
- Structure-Function Relationship as the Foundation for Cardiac Myosin Inhibition in Hypertrophic Cardiomyopathy.Circulation · 2026Article
- Probing relaxed myosin states in hypertrophic cardiomyopathy by second harmonic-generation microscopy.eLife · 2026Article
- AMPKγ2 Meets Myosin: A New Link Between Metabolism and Sarcomere Function.Circulation research · 2026Article
- Thick filament molecular interfaces play a critical role in the pathogenesis of hypertrophic cardiomyopathy.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- The E525K β-Myosin Mutation Causes Hypocontractility in Cardiomyocytes Without Altering Loaded Crossbridge Cycling.bioRxiv : the preprint server for biology · 2026Article
- Mavacamten shows broad benefit in human and mouse models of MYBPC3-related hypertrophic cardiomyopathy.Nature cardiovascular research · 2026Article
- Force-Induced Ankle Opening Reveals Mechanical Stabilization of the Ankle of Human β-Cardiac Myosin.ACS nano · 2026Article
- Subsarcomeric regulation of thin and thick filaments in skeletal muscle myofibrils.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- The hypertrophic cardiomyopathy mutation G768R makes cardiac myosin a high duty ratio motor.bioRxiv : the preprint server for biology · 2026Article
- Severe obesity in human HFpEF alters contractile protein function and organization.Science (New York, N.Y.) · 2026Article
- Dynamics of the β-cardiac myosin auto-inhibited state explain cardiomyopathy pathogenesis.Nature communications · 2026Article
- The hypertrophic cardiomyopathy myosin variant G256E prolongs cardiac muscle relaxation via altered nucleotide handling.Communications chemistry · 2026Article
- Cryo-EM reveals how cardiomyopathy therapeutic drugs modulate the myosin motors of the heart.Science advances · 2026Article
- Cryo-EM structure of shutdown human nonmuscle myosin 2A.Science advances · 2026Article
- A Novel Bacteriocin from Insectivorous Bat (Hipposideros speoris) Intestine Mimicking Mammalian FAM216B: Probiotic, Antioxidant, and Antimicrobial Properties of Enterococcus hirae BNT6.Probiotics and antimicrobial proteins · 2026Article
- Creating an atlas of variant effects to resolve variants of uncertain significance and guide cardiovascular medicine.Nature reviews. Cardiology · 2026Review
- Multi-omics Insight into Cardiac Myofibril Remodeling in Post-Prandial Burmese Pythons.bioRxiv : the preprint server for biology · 2026Article
- Comparing cryo-EM structures of the vertebrate cardiac muscle thick filament.Biophysical reviews · 2026Article
- Cryo-EM Reveals How Cardiomyopathy Therapeutic Drugs Modulate the Myosin Motors of the Heart.bioRxiv : the preprint server for biology · 2025Article
- The G256E HCM mutation prolongs cardiac muscle relaxation via altered nucleotide handling.Research square · 2025Article
93 more citing papers are in PubMed but not listed here.
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
Hypertrophic cardiomyopathy (HCM) is primarily caused by mutations in β-cardiac myosin and myosin-binding protein-C (MyBP-C). Changes in the contractile parameters of myosin measured so far do not explain the clinical hypercontractility caused by such mutations. We propose that hypercontractility is due to an increase in the number of myosin heads (S1) that are accessible for force production. In support of this hypothesis, we demonstrate myosin tail (S2)-dependent functional regulation of actin-activated human β-cardiac myosin ATPase. In addition, we show that both S2 and MyBP-C bind to S1 and that phosphorylation of either S1 or MyBP-C weakens these interactions. Importantly, the S1-S2 interaction is also weakened by four myosin HCM-causing mutations but not by two other mutations. To explain these experimental results, we propose a working structural model involving multiple interactions, including those with myosin's own S2 and MyBP-C, that hold myosin in a sequestered state.
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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.