ArticleJournal of molecular biology2008
Three-dimensional reconstruction of tarantula myosin filaments suggests how phosphorylation may regulate myosin activity.
Article in Journal of molecular biology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 121 papers.
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121 citing papers in PubMed, 156 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
- Structural basis of nonmuscle myosin-2 autoinhibition mechanisms.Nature communications · 2026Article
- The thin line between biochemistry and structure where myosin super relaxed state lies.Biophysical reviews · 2026Review
- "QuickStainer": a rapid negative staining device for improved preservation of molecular structure.Journal of structural biology · 2026Article
- Cryo-EM reveals how cardiomyopathy therapeutic drugs modulate the myosin motors of the heart.Science advances · 2026Article
- Spatial control of myosin regulatory light chain phosphorylation modulates cardiac thick filament mechanosensing.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Human atrial skinned muscle fibers exhibit reduced length-dependent activation but show faster force development kinetics than ventricular muscle.Journal of molecular and cellular cardiology · 2026Article
- Comparing cryo-EM structures of the vertebrate cardiac muscle thick filament.Biophysical reviews · 2026Article
- Structure of the Myosin Thick Filaments in Muscle.Sub-cellular biochemistry · 2026Review
- Cryo-EM Reveals How Cardiomyopathy Therapeutic Drugs Modulate the Myosin Motors of the Heart.bioRxiv : the preprint server for biology · 2025Article
- Structural basis of nonmuscle myosin-2 autoinhibition mechanisms.bioRxiv : the preprint server for biology · 2025Article
- Myosin 2 - A general contractor for the cytoskeleton.Current opinion in cell biology · 2025Review
- The Mechanism of Modulation of Cardiac Force by Temperature.International journal of molecular sciences · 2025Article
- Reassessing the unifying hypothesis for hypercontractility caused by myosin mutations in hypertrophic cardiomyopathy.The EMBO journal · 2024Review
- Cardiac length-dependent activation driven by force-dependent thick-filament dynamics.Biophysical journal · 2024Article
- Multiscale modeling shows how 2'-deoxy-ATP rescues ventricular function in heart failure.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- Structure, regulation, and mechanisms of nonmuscle myosin-2.Cellular and molecular life sciences : CMLS · 2024Review
- Myosin folding boosts solubility in cardiac muscle sarcomeres.JCI insight · 2024Article
- Myofilament dysfunction in diastolic heart failure.Heart failure reviews · 2024Review
- Article
61 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
Muscle contraction involves the interaction of the myosin heads of the thick filaments with actin subunits of the thin filaments. Relaxation occurs when this interaction is blocked by molecular switches on these filaments. In many muscles, myosin-linked regulation involves phosphorylation of the myosin regulatory light chains (RLCs). Electron microscopy of vertebrate smooth muscle myosin molecules (regulated by phosphorylation) has provided insight into the relaxed structure, revealing that myosin is switched off by intramolecular interactions between its two heads, the free head and the blocked head. Three-dimensional reconstruction of frozen-hydrated specimens revealed that this asymmetric head interaction is also present in native thick filaments of tarantula striated muscle. Our goal in this study was to elucidate the structural features of the tarantula filament involved in phosphorylation-based regulation. A new reconstruction revealed intra- and intermolecular myosin interactions in addition to those seen previously. To help interpret the interactions, we sequenced the tarantula RLC and fitted an atomic model of the myosin head that included the predicted RLC atomic structure and an S2 (subfragment 2) crystal structure to the reconstruction. The fitting suggests one intramolecular interaction, between the cardiomyopathy loop of the free head and its own S2, and two intermolecular interactions, between the cardiac loop of the free head and the essential light chain of the blocked head and between the Leu305-Gln327 interaction loop of the free head and the N-terminal fragment of the RLC of the blocked head. These interactions, added to those previously described, would help switch off the thick filament. Molecular dynamics simulations suggest how phosphorylation could increase the helical content of the RLC N-terminus, weakening these interactions, thus releasing both heads and activating the thick filament.
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