ArticleProceedings of the National Academy of Sciences of the United States of America2010
Cardiomyopathy-linked myosin regulatory light chain mutations disrupt myosin strain-dependent biochemistry.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.
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Who cites it
63 citing papers in PubMed, 81 citations in OpenAlex.
- Article
- Motility Assay to Probe the Calcium Sensitivity of Myosin and Regulated Thin Filaments.Methods in molecular biology (Clifton, N.J.) · 2024Article
- Phosphorylation Mimetic of Myosin Regulatory Light Chain Mitigates Cardiomyopathy-Induced Myofilament Impairment in Mouse Models of RCM and DCM.Life (Basel, Switzerland) · 2023Article
- Article
- Bridging the muscle genome to phenome across multiple biological scales.The Journal of experimental biology · 2022Article
- Hypertrophic cardiomyopathy: Mutations to mechanisms to therapies.Frontiers in physiology · 2022Review
- Functional comparison of phosphomimetic S15D and T160D mutants of myosin regulatory light chain exchanged in cardiac muscle preparations of HCM and WT mice.Frontiers in cardiovascular medicine · 2022Article
- Cardiac myosin contraction and mechanotransduction in health and disease.The Journal of biological chemistry · 2021Review
- Impact of regulatory light chain mutation K104E on the ATPase and motor properties of cardiac myosin.The Journal of general physiology · 2021Article
- Mechanical dysfunction of the sarcomere induced by a pathogenic mutation in troponin T drives cellular adaptation.The Journal of general physiology · 2021Article
- Regulatory Light Chains in Cardiac Development and Disease.International journal of molecular sciences · 2021Review
- Complexity in genetic cardiomyopathies and new approaches for mechanism-based precision medicine.The Journal of general physiology · 2021Article
- Mavacamten decreases maximal force and CaAmerican journal of physiology. Heart and circulatory physiology · 2021Article
- Opposing Pressures of Speed and Efficiency Guide the Evolution of Molecular Machines.Molecular biology and evolution · 2019Article
- Disrupted mechanobiology links the molecular and cellular phenotypes in familial dilated cardiomyopathy.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Allele-Specific Silencing Ameliorates Restrictive Cardiomyopathy Attributable to a Human Myosin Regulatory Light Chain Mutation.Circulation · 2019Article
- Exploring the Continuum of Hypertrophic Cardiomyopathy-From DNA to Clinical Expression.Medicina (Kaunas, Lithuania) · 2019Review
- Hereditary heart disease: pathophysiology, clinical presentation, and animal models of HCM, RCM, and DCM associated with mutations in cardiac myosin light chains.Pflugers Archiv : European journal of physiology · 2019Review
- Slow-twitch skeletal muscle defects accompany cardiac dysfunction in transgenic mice with a mutation in the myosin regulatory light chain.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2019Article
- Regulatory light chain phosphorylation augments length-dependent contraction in PTU-treated rats.The Journal of general physiology · 2019Article
3 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Familial hypertrophic cardiomyopathy (FHC) is caused by mutations in sarcomeric proteins including the myosin regulatory light chain (RLC). Two such FHC mutations, R58Q and N47K, located near the cationic binding site of the RLC, have been identified from population studies. To examine the molecular basis for the observed phenotypes, we exchanged endogenous RLC from native porcine cardiac myosin with recombinant human ventricular wild type (WT) or FHC mutant RLC and examined the ability of the reconstituted myosin to propel actin filament sliding using the in vitro motility assay. We find that, whereas the mutant myosins are indistinguishable from the controls (WT or native myosin) under unloaded conditions, both R58Q- and N47K-exchanged myosins show reductions in force and power output compared with WT or native myosin. We also show that the changes in loaded kinetics are a result of mutation-induced loss of myosin strain sensitivity of ADP affinity. We propose that the R58Q and N47K mutations alter the mechanical properties of the myosin neck region, leading to altered load-dependent kinetics that may explain the observed mutant-induced FHC phenotypes.
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Registered trials
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.