ArticleProceedings of the National Academy of Sciences of the United States of America2016
C0 and C1 N-terminal Ig domains of myosin binding protein C exert different effects on thin filament activation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers.
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Who cites it
40 citing papers in PubMed, 60 citations in OpenAlex.
- Myosin-binding protein C slows cardiac myofibril relaxation kinetics.The Journal of physiology · 2025Article
- Interaction of cardiac leiomodin with the native cardiac thin filament.PLoS biology · 2025Article
- Duality in disease: How two amino acid substitutions at actin residue 312 result in opposing forms of cardiomyopathy.The Journal of biological chemistry · 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
- Troponin Structural Dynamics in the Native Cardiac Thin Filament Revealed by Cryo Electron Microscopy.Journal of molecular biology · 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
- Hypertrophic cardiomyopathy inThe journal of cardiovascular aging · 2024Article
- Cryo-electron tomography of intact cardiac muscle reveals myosin binding protein-C linking myosin and actin filaments.Journal of muscle research and cell motility · 2023Article
- Hypertrophic cardiomyopathy in purpose-bred cats with the A31P mutation in cardiac myosin binding protein-C.Scientific reports · 2023Article
- cMyBP-C ablation in human engineered cardiac tissue causes progressive Ca2+-handling abnormalities.The Journal of general physiology · 2023Article
- In situ FRET-based localization of the N terminus of myosin binding protein-C in heart muscle cells.Proceedings of the National Academy of Sciences of the United States of America · 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
- GSK-3β Localizes to the Cardiac Z-Disc to Maintain Length Dependent Activation.Circulation research · 2022Article
- Interaction of the C2 Ig-like Domain of Cardiac Myosin Binding Protein-C with F-actin.Journal of molecular biology · 2021Article
- Cardiac MyBP-C phosphorylation regulates the Frank-Starling relationship in murine hearts.The Journal of general physiology · 2021Article
- cMyBP-C phosphorylation modulates the time-dependent slowing of unloaded shortening in murine skinned myocardium.The Journal of general physiology · 2021Article
- Making waves: A proposed new role for myosin-binding protein C in regulating oscillatory contractions in vertebrate striated muscle.The Journal of general physiology · 2021Article
- In the eye of the STORM: Tracking the myosin-binding protein C N terminus in heart muscle.The Journal of general physiology · 2021Article
- A high-throughput fluorescence lifetime-based assay to detect binding of myosin-binding protein C to F-actin.The Journal of general physiology · 2021Article
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Mutations in genes encoding myosin, the molecular motor that powers cardiac muscle contraction, and its accessory protein, cardiac myosin binding protein C (cMyBP-C), are the two most common causes of hypertrophic cardiomyopathy (HCM). Recent studies established that the N-terminal domains (NTDs) of cMyBP-C (e.g., C0, C1, M, and C2) can bind to and activate or inhibit the thin filament (TF). However, the molecular mechanism(s) by which NTDs modulate interaction of myosin with the TF remains unknown and the contribution of each individual NTD to TF activation/inhibition is unclear. Here we used an integrated structure-function approach using cryoelectron microscopy, biochemical kinetics, and force measurements to reveal how the first two Ig-like domains of cMyPB-C (C0 and C1) interact with the TF. Results demonstrate that despite being structural homologs, C0 and C1 exhibit different patterns of binding on the surface of F-actin. Importantly, C1 but not C0 binds in a position to activate the TF by shifting tropomyosin (Tm) to the "open" structural state. We further show that C1 directly interacts with Tm and traps Tm in the open position on the surface of F-actin. Both C0 and C1 compete with myosin subfragment 1 for binding to F-actin and effectively inhibit actomyosin interactions when present at high ratios of NTDs to F-actin. Finally, we show that in contracting sarcomeres, the activating effect of C1 is apparent only once low levels of Ca(2+) have been achieved. We suggest that Ca(2+) modulates the interaction of cMyBP-C with the TF in the sarcomere.
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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.