ArticleProceedings of the National Academy of Sciences of the United States of America2019
Revealing the mechanism of how cardiac myosin-binding protein C N-terminal fragments sensitize thin filaments for myosin binding.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.
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Who cites it
34 citing papers in PubMed, 1 synthesis or guideline pooled it, 57 citations in OpenAlex.
- Implications of S-glutathionylation of sarcomere proteins in cardiac disorders, therapies, and diagnosis.Frontiers in cardiovascular medicine · 2022Pooled it
- Myosin-binding protein C slows cardiac myofibril relaxation kinetics.The Journal of physiology · 2025Article
- Autoinhibition of cMyBP-C by its middle domains.Journal of molecular and cellular cardiology · 2025Article
- 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
- The D75N and P161S Mutations in the C0-C2 Fragment of cMyBP-C Associated with Hypertrophic Cardiomyopathy Disturb the Thin Filament Activation, Nucleotide Exchange in Myosin, and Actin-Myosin Interaction.International journal of molecular sciences · 2024Article
- Reassessing the unifying hypothesis for hypercontractility caused by myosin mutations in hypertrophic cardiomyopathy.The EMBO journal · 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
- Missense mutations in the central domains of cardiac myosin binding protein-C and their potential contribution to hypertrophic cardiomyopathy.The Journal of biological chemistry · 2024Article
- The Relationship between Changes inJournal of cardiovascular development and disease · 2023Review
- The contribution of N-terminal truncated cMyBPC to in vivo cardiac function.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
- Single-molecule imaging reveals how mavacamten and PKA modulate ATP turnover in skeletal muscle myofibrils.The Journal of general physiology · 2023Article
- Cryo-Electron Microscopy Reveals Cardiac Myosin Binding Protein-C M-Domain Interactions with the Thin Filament.Journal of molecular biology · 2022Article
- Nanosurfer assay dissects β-cardiac myosin and cardiac myosin-binding protein C interactions.Biophysical journal · 2022Article
- Targeting the sarcomere in inherited cardiomyopathies.Nature reviews. Cardiology · 2022Review
- Human cardiac myosin-binding protein C phosphorylation- and mutation-dependent structural dynamics monitored by time-resolved FRET.Journal of molecular and cellular cardiology · 2022Article
- Myofilament glycation in diabetes reduces contractility by inhibiting tropomyosin movement, is rescued by cMyBPC domains.Journal of molecular and cellular cardiology · 2022Article
- Actomyosin Complex.Sub-cellular biochemistry · 2022Article
- Natural variant frequencies across domains from different sarcomere proteins cross-correlate to identify inter-protein contacts associated with cardiac muscle function and disease.Molecular biomedicine · 2021Article
- Assessment of the Contribution of a Thermodynamic and Mechanical Destabilization of Myosin-Binding Protein C Domain C2 to the Pathomechanism of Hypertrophic Cardiomyopathy-Causing Double MutationInternational journal of molecular sciences · 2021Article
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Cardiac muscle contraction is triggered by calcium binding to troponin. The consequent movement of tropomyosin permits myosin binding to actin, generating force. Cardiac myosin-binding protein C (cMyBP-C) plays a modulatory role in this activation process. One potential mechanism for the N-terminal domains of cMyBP-C to achieve this is by binding directly to the actin-thin filament at low calcium levels to enhance the movement of tropomyosin. To determine the molecular mechanisms by which cMyBP-C enhances myosin recruitment to the actin-thin filament, we directly visualized fluorescently labeled cMyBP-C N-terminal fragments and GFP-labeled myosin molecules binding to suspended actin-thin filaments in a fluorescence-based single-molecule microscopy assay. Binding of the C0C3 N-terminal cMyBP-C fragment to the thin filament enhanced myosin association at low calcium levels. However, at high calcium levels, C0C3 bound in clusters, blocking myosin binding. Dynamic imaging of thin filament-bound Cy3-C0C3 molecules demonstrated that these fragments diffuse along the thin filament before statically binding, suggesting a mechanism that involves a weak-binding mode to search for access to the thin filament and a tight-binding mode to sensitize the thin filament to calcium, thus enhancing myosin binding. Although shorter N-terminal fragments (Cy3-C0C1 and Cy3-C0C1f) bound to the thin filaments and displayed modes of motion on the thin filament similar to that of the Cy3-C0C3 fragment, the shorter fragments were unable to sensitize the thin filament. Therefore, the longer N-terminal fragment (C0C3) must possess the requisite domains needed to bind specifically to the thin filament in order for the cMyBP-C N terminus to modulate cardiac contractility.
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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.