ArticleProceedings of the National Academy of Sciences of the United States of America2017
Phosphorylation of cardiac myosin binding protein C releases myosin heads from the surface of cardiac thick filaments.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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Who cites it
61 citing papers in PubMed, 91 citations in OpenAlex.
- Fast skeletal myosin binding protein-C expression exacerbates dysfunction in heart failure.Basic research in cardiology · 2026Article
- Comparing cryo-EM structures of the vertebrate cardiac muscle thick filament.Biophysical reviews · 2026Article
- Annotating the x-ray diffraction pattern of vertebrate striated muscle.Biophysical journal · 2025Article
- Myocardium From Patients With ATTR Amyloidosis Produces Less Force Secondary to Increased Fibrosis.JACC. Basic to translational science · 2025Article
- Research into the physiology of myosins - a personal odyssey.European journal of translational myology · 2025Article
- cMyBP-C in hypertrophic cardiomyopathy: gene therapy and small-molecule innovations.Frontiers in cardiovascular medicine · 2025Review
- An integrated picture of the structural pathways controlling the heart performance.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Interacting myosin head dynamics and their modification by 2'-deoxy-ADP.Biophysical journal · 2024Article
- Alterations in cardiac contractile and regulatory proteins contribute to age-related cardiac dysfunction in male rats.Physiological reports · 2024Article
- Cardiac myosin binding protein-C phosphorylation as a function of multiple protein kinase and phosphatase activities.Nature communications · 2024Article
- Structure of mavacamten-free human cardiac thick filaments within the sarcomere by cryoelectron tomography.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Mechanism-based myofilament manipulation to treat diastolic dysfunction in HFpEF.Frontiers in physiology · 2024Review
- Cardiac myosin-binding protein C N-terminal interactions with myosin and actin filaments: Opposite effects of phosphorylation and M-domain mutations.Journal of molecular and cellular cardiology · 2024Article
- Discovery of a novel cardiac-specific myosin modulator using artificial intelligence-based virtual screening.Nature communications · 2023Article
- The structural and functional integrities of porcine myocardium are mostly preserved by cryopreservation.The Journal of general physiology · 2023Article
- cMyBP-C ablation in human engineered cardiac tissue causes progressive Ca2+-handling abnormalities.The Journal of general physiology · 2023Article
- Etiology of genetic muscle disorders induced by mutations in fast and slow skeletal MyBP-C paralogs.Experimental & molecular medicine · 2023Review
- Cryo-Electron Microscopy Reveals Cardiac Myosin Binding Protein-C M-Domain Interactions with the Thin Filament.Journal of molecular biology · 2022Article
- NEB mutations disrupt the super-relaxed state of myosin and remodel the muscle metabolic proteome in nemaline myopathy.Acta neuropathologica communications · 2022Article
- Distinct Mechanisms for Increased Cardiac Contraction Through Selective Alteration of Either Myosin or Troponin Activity.JACC. Basic to translational science · 2022Article
1 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors at 3 institutions in 2 countries.
Funding
Abstract
Cardiac myosin binding protein C (cMyBP-C) has a key regulatory role in cardiac contraction, but the mechanism by which changes in phosphorylation of cMyBP-C accelerate cross-bridge kinetics remains unknown. In this study, we isolated thick filaments from the hearts of mice in which the three serine residues (Ser273, Ser282, and Ser302) that are phosphorylated by protein kinase A in the m-domain of cMyBP-C were replaced by either alanine or aspartic acid, mimicking the fully nonphosphorylated and the fully phosphorylated state of cMyBP-C, respectively. We found that thick filaments from the cMyBP-C phospho-deficient hearts had highly ordered cross-bridge arrays, whereas the filaments from the cMyBP-C phospho-mimetic hearts showed a strong tendency toward disorder. Our results support the hypothesis that dephosphorylation of cMyBP-C promotes or stabilizes the relaxed/superrelaxed quasi-helical ordering of the myosin heads on the filament surface, whereas phosphorylation weakens this stabilization and binding of the heads to the backbone. Such structural changes would modulate the probability of myosin binding to actin and could help explain the acceleration of cross-bridge interactions with actin when cMyBP-C is phosphorylated because of, for example, activation of β
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