ArticleThe Journal of biological chemistry2015
Mechanistic heterogeneity in contractile properties of α-tropomyosin (TPM1) mutants associated with inherited cardiomyopathies.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 51 citations in OpenAlex.
- A novel missense mutation in tropomyosin 1 gene associated with hypertrophic cardiomyopathy.Journal, genetic engineering & biotechnology · 2026Article
- Article
- Distinct mechanisms drive divergent phenotypes in hypertrophic and dilated cardiomyopathy-associated TPM1 variants.The Journal of clinical investigation · 2024Article
- Obstructive hypertrophic cardiomyopathy: from genetic insights to a multimodal therapeutic approach with mavacamten, aficamten, and beyond.The Egyptian heart journal : (EHJ) : official bulletin of the Egyptian Society of Cardiology · 2024Review
- Novel Mutation Lys30Glu in theInternational journal of molecular sciences · 2024Article
- Novel Mutation Glu98Lys in Cardiac Tropomyosin Alters Its Structure and Impairs Myocardial Relaxation.International journal of molecular sciences · 2023Article
- Sarcomeric gene variants among Indians with hypertrophic cardiomyopathy: A scoping review.The Indian journal of medical research · 2023Article
- Mechanisms of pathogenicity in the hypertrophic cardiomyopathy-associated TPM1 variant S215L.PNAS nexus · 2023Article
- Impact of Troponin in Cardiomyopathy Development Caused by Mutations in Tropomyosin.International journal of molecular sciences · 2022Article
- Hypertrophic cardiomyopathy: Mutations to mechanisms to therapies.Frontiers in physiology · 2022Review
- Thin filament cardiomyopathies: A review of genetics, disease mechanisms, and emerging therapeutics.Frontiers in cardiovascular medicine · 2022Review
- Functional enrichment of alternative splicing events with NEASE reveals insights into tissue identity and diseases.Genome biology · 2021Article
- Molecular Genetic Basis of Hypertrophic Cardiomyopathy.Circulation research · 2021Article
- Proteomic Sequencing of Stellate Ganglions in Rabbits With Myocardial Infarction.Frontiers in physiology · 2021Article
- Modulating the tension-time integral of the cardiac twitch prevents dilated cardiomyopathy in murine hearts.JCI insight · 2020Article
- Visualizing the in vitro assembly of tropomyosin/actin filaments using TIRF microscopy.Biophysical reviews · 2020Review
- Genetic Dissection of Hypertrophic Cardiomyopathy with Myocardial RNA-Seq.International journal of molecular sciences · 2020Article
- Thin filament dysfunctions caused by mutations in tropomyosin Tpm3.12 and Tpm1.1.Journal of muscle research and cell motility · 2020Review
- KBTBD13 and the ever-expanding sarcomeric universe.The Journal of clinical investigation · 2020Article
- Cardiomyopathy-associated mutations in tropomyosin differently affect actin-myosin interaction at single-molecule and ensemble levels.Journal of muscle research and cell motility · 2019Review
Corrections and comments
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Authors and funding
15 authors at 5 institutions in 2 countries.
Funding
Abstract
The most frequent known causes of primary cardiomyopathies are mutations in the genes encoding sarcomeric proteins. Among those are 30 single-residue mutations in TPM1, the gene encoding α-tropomyosin. We examined seven mutant tropomyosins, E62Q, D84N, I172T, L185R, S215L, D230N, and M281T, that were chosen based on their clinical severity and locations along the molecule. The goal of our study was to determine how the biochemical characteristics of each of these mutant proteins are altered, which in turn could provide a structural rationale for treatment of the cardiomyopathies they produce. Measurements of Ca(2+) sensitivity of human β-cardiac myosin ATPase activity are consistent with the hypothesis that hypertrophic cardiomyopathies are hypersensitive to Ca(2+) activation, and dilated cardiomyopathies are hyposensitive. We also report correlations between ATPase activity at maximum Ca(2+) concentrations and conformational changes in TnC measured using a fluorescent probe, which provide evidence that different substitutions perturb the structure of the regulatory complex in different ways. Moreover, we observed changes in protein stability and protein-protein interactions in these mutants. Our results suggest multiple mechanistic pathways to hypertrophic and dilated cardiomyopathies. Finally, we examined a computationally designed mutant, E181K, that is hypersensitive, confirming predictions derived from in silico structural analysis.
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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.