ArticleFrontiers in physiology2014
Structural and protein interaction effects of hypertrophic and dilated cardiomyopathic mutations in alpha-tropomyosin.
Article in Frontiers in physiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 14 citations in OpenAlex.
- Effects of Cardiomyopathic Mutations on the Cytoplasmic Tropomyosin Isoform Tpm1.7.Molecules (Basel, Switzerland) · 2026Article
- Distinct mechanisms drive divergent phenotypes in hypertrophic and dilated cardiomyopathy-associated TPM1 variants.The Journal of clinical investigation · 2024Article
- Mechanisms of pathogenicity in the hypertrophic cardiomyopathy-associated TPM1 variant S215L.PNAS nexus · 2023Article
- Loss of crossbridge inhibition drives pathological cardiac hypertrophy in patients harboring the TPM1 E192K mutation.The Journal of general physiology · 2021Article
- The Effect of Tropomyosin Mutations on Actin-Tropomyosin Binding: In Search of Lost Time.Biophysical journal · 2019Article
- Moving beyond simple answers to complex disorders in sarcomeric cardiomyopathies: the role of integrated systems.Pflugers Archiv : European journal of physiology · 2019Review
- Fropofol decreases force development in cardiac muscle.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2018Article
- Biophysical Derangements in Genetic Cardiomyopathies.Heart failure clinics · 2018Review
- Structural destabilization of tropomyosin induced by the cardiomyopathy-linked mutation R21H.Protein science : a publication of the Protein Society · 2018Article
- Insights and Challenges of Multi-Scale Modeling of Sarcomere Mechanics in cTn and Tm DCM Mutants-Genotype to Cellular Phenotype.Frontiers in physiology · 2017Review
- Investigating the effects of tropomyosin mutations on its flexibility and interactions with filamentous actin using molecular dynamics simulation.Journal of muscle research and cell motility · 2016Article
- Cardiac Troponin and Tropomyosin: Structural and Cellular Perspectives to Unveil the Hypertrophic Cardiomyopathy Phenotype.Frontiers in physiology · 2016Review
Corrections and comments
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Authors and funding
5 authors at 4 institutions in 1 country.
Funding
Abstract
The potential alterations to structure and associations with thin filament proteins caused by the dilated cardiomyopathy (DCM) associated tropomyosin (Tm) mutants E40K and E54K, and the hypertrophic cardiomyopathy (HCM) associated Tm mutants E62Q and L185R, were investigated. In order to ascertain what the cause of the known functional effects may be, structural and protein-protein interaction studies were conducted utilizing actomyosin ATPase activity measurements and spectroscopy. In actomyosin ATPase measurements, both HCM mutants and the DCM mutant E54K caused increases in Ca(2+)-induced maximal ATPase activities, while E40K caused a decrease. Investigation of Tm's ability to inhibit actomyosin ATPase in the absence of troponin showed that HCM-associated mutant Tms did not inhibit as well as wildtype, whereas the DCM associated mutant E40K inhibited better. E54K did not inhibit the actomyosin ATPase activity at any concentration of Tm tested. Thermal denaturation studies by circular dichroism and molecular modeling of the mutations in Tm showed that in general, the DCM mutants caused localized destabilization of the Tm dimers, while the HCM mutants resulted in increased stability. These findings demonstrate that the structural alterations in Tm observed here may affect the regulatory function of Tm on actin, thereby directly altering the ATPase rates of myosin.
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