ArticleJournal of molecular biology2016
Conserved Intramolecular Interactions Maintain Myosin Interacting-Heads Motifs Explaining Tarantula Muscle Super-Relaxed State Structural Basis.
Article in Journal of molecular biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 72 papers.
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Who cites it
72 citing papers in PubMed, 100 citations in OpenAlex.
- 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
- Cryo-EM reveals how cardiomyopathy therapeutic drugs modulate the myosin motors of the heart.Science advances · 2026Article
- Destabilization of cardiac myosin acetylation and sequestration with type 2 diabetes mellitus.Cardiovascular diabetology · 2026Article
- Cryo-EM Reveals How Cardiomyopathy Therapeutic Drugs Modulate the Myosin Motors of the Heart.bioRxiv : the preprint server for biology · 2025Article
- Tailored therapeutics for cardiomyopathies.Nature reviews. Cardiology · 2025Review
- Heterogeneous Dysregulation of Myosin Super-Relaxation and Energetics in Hypertrophic Cardiomyopathy.Circulation. Heart failure · 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
- Dysregulated skeletal muscle myosin super-relaxation and energetics in male participants with type 2 diabetes mellitus.Diabetologia · 2025Article
- Structure of the Inhibited Smooth Muscle Myosin and Its Implications on the Regulation of Insect Striated Muscle Myosin.Life (Basel, Switzerland) · 2025Review
- Interacting myosin head dynamics and their modification by 2'-deoxy-ADP.Biophysical journal · 2024Article
- Aficamten is a small-molecule cardiac myosin inhibitor designed to treat hypertrophic cardiomyopathy.Nature cardiovascular research · 2024Article
- Super-relaxed myosins contribute to respiratory muscle hibernation in mechanically ventilated patients.Science translational medicine · 2024Article
- A Laing distal myopathy-associated proline substitution in the β-myosin rod perturbs myosin cross-bridging activity.The Journal of clinical investigation · 2024Article
- Bringing into focus the central domains C3-C6 of myosin binding protein C.Frontiers in physiology · 2024Review
- The biochemically defined super relaxed state of myosin-A paradox.The Journal of biological chemistry · 2024Article
- Article
- Physical activity impacts resting skeletal muscle myosin conformation and lowers its ATP consumption.The Journal of general physiology · 2023Article
- Cryo-EM structure of the folded-back state of human β-cardiac myosin.Nature communications · 2023Article
- Myofilament-associated proteins with intrinsic disorder (MAPIDs) and their resolution by computational modeling.Quarterly reviews of biophysics · 2023Review
- Variants of the myosin interacting-heads motif.The Journal of general physiology · 2023Article
12 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 4 institutions in 3 countries.
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Abstract
Tarantula striated muscle is an outstanding system for understanding the molecular organization of myosin filaments. Three-dimensional reconstruction based on cryo-electron microscopy images and single-particle image processing revealed that, in a relaxed state, myosin molecules undergo intramolecular head-head interactions, explaining why head activity switches off. The filament model obtained by rigidly docking a chicken smooth muscle myosin structure to the reconstruction was improved by flexibly fitting an atomic model built by mixing structures from different species to a tilt-corrected 2-nm three-dimensional map of frozen-hydrated tarantula thick filament. We used heavy and light chain sequences from tarantula myosin to build a single-species homology model of two heavy meromyosin interacting-heads motifs (IHMs). The flexibly fitted model includes previously missing loops and shows five intramolecular and five intermolecular interactions that keep the IHM in a compact off structure, forming four helical tracks of IHMs around the backbone. The residues involved in these interactions are oppositely charged, and their sequence conservation suggests that IHM is present across animal species. The new model, PDB 3JBH, explains the structural origin of the ATP turnover rates detected in relaxed tarantula muscle by ascribing the very slow rate to docked unphosphorylated heads, the slow rate to phosphorylated docked heads, and the fast rate to phosphorylated undocked heads. The conservation of intramolecular interactions across animal species and the presence of IHM in bilaterians suggest that a super-relaxed state should be maintained, as it plays a role in saving ATP in skeletal, cardiac, and smooth muscles.
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