ArticleProceedings of the National Academy of Sciences of the United States of America2013
Structural basis of the relaxed state of a Ca2+-regulated myosin filament and its evolutionary implications.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.
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Who cites it
41 citing papers in PubMed, 52 citations in OpenAlex.
- Reassessing the unifying hypothesis for hypercontractility caused by myosin mutations in hypertrophic cardiomyopathy.The EMBO journal · 2024Review
- From amoeboid myosin to unique targeted medicines for a genetic cardiac disease.Frontiers in physiology · 2024Review
- Variants of the myosin interacting-heads motif.The Journal of general physiology · 2023Article
- Structure of the Flight Muscle Thick Filament from the Bumble Bee,International journal of molecular sciences · 2022Article
- Interacting-heads motif explains the X-ray diffraction pattern of relaxed vertebrate skeletal muscle.Biophysical journal · 2022Article
- Structural basis of the super- and hyper-relaxed states of myosin II.The Journal of general physiology · 2022Review
- Actomyosin Complex.Sub-cellular biochemistry · 2022Article
- Cardiac myosin super relaxation (SRX): a perspective on fundamental biology, human disease and therapeutics.Biology open · 2021Review
- Article
- The mesa trail and the interacting heads motif of myosin II.Archives of biochemistry and biophysics · 2020Article
- The central role of the tail in switching off 10S myosin II activity.The Journal of general physiology · 2019Article
- β-Cardiac myosin hypertrophic cardiomyopathy mutations release sequestered heads and increase enzymatic activity.Nature communications · 2019Article
- Three perspectives on the molecular basis of hypercontractility caused by hypertrophic cardiomyopathy mutations.Pflugers Archiv : European journal of physiology · 2019Review
- Lessons from a tarantula: new insights into myosin interacting-heads motif evolution and its implications on disease.Biophysical reviews · 2018Review
- Mavacamten stabilizes an autoinhibited state of two-headed cardiac myosin.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Titin-mediated thick filament activation stabilizes myofibrils on the descending limb of their force-length relationship.Journal of sport and health science · 2018Article
- Differences between fast and slow muscles in scallops revealed through proteomics and transcriptomics.BMC genomics · 2018Article
- Interacting-heads motif has been conserved as a mechanism of myosin II inhibition since before the origin of animals.Proceedings of the National Academy of Sciences of the United States of America · 2018Article
- Hypertrophic cardiomyopathy and the myosin mesa: viewing an old disease in a new light.Biophysical reviews · 2018Review
- Omecamtiv mercabil and blebbistatin modulate cardiac contractility by perturbing the regulatory state of the myosin filament.The Journal of physiology · 2018Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Myosin filaments of muscle are regulated either by phosphorylation of their regulatory light chains or Ca(2+) binding to the essential light chains, contributing to on-off switching or modulation of contraction. Phosphorylation-regulated filaments in the relaxed state are characterized by an asymmetric interaction between the two myosin heads, inhibiting their actin binding or ATPase activity. Here, we have tested whether a similar interaction switches off activity in myosin filaments regulated by Ca(2+) binding. Cryo-electron microscopy and single-particle image reconstruction of Ca(2+)-regulated (scallop) filaments reveals a helical array of myosin head-pair motifs above the filament surface. Docking of atomic models of scallop myosin head domains into the motifs reveals that the heads interact in a similar way to those in phosphorylation-regulated filaments. The results imply that the two major evolutionary branches of myosin regulation--involving phosphorylation or Ca(2+) binding--share a common structural mechanism for switching off thick-filament activity in relaxed muscle. We suggest that the Ca(2+)-binding mechanism evolved from the more ancient phosphorylation-based system to enable rapid response of myosin-regulated muscles to activation. Although the motifs are similar in both systems, the scallop structure is more tilted and higher above the filament backbone, leading to different intermolecular interactions. The reconstruction reveals how the myosin tail emerges from the motif, connecting the heads to the filament backbone, and shows that the backbone is built from supramolecular assemblies of myosin tails. The reconstruction provides a native structural context for understanding past biochemical and biophysical studies of this model Ca(2+)-regulated myosin.
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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.