ArticleJournal of molecular biology2012
Molecular effects of familial hypertrophic cardiomyopathy-related mutations in the TNT1 domain of cTnT.
Article in Journal of molecular biology, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.
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Who cites it
29 citing papers in PubMed, 1 synthesis or guideline pooled it, 35 citations in OpenAlex.
- Meta-analysis of cardiomyopathy-associated variants in troponin genes identifies loci and intragenic hot spots that are associated with worse clinical outcomes.Journal of molecular and cellular cardiology · 2020Pooled it
- Mechanism of RNA Oxidation and Its Inhibitor Involved in Ang II-Induced Cardiomyocyte Hypertrophy.Aging medicine (Milton (N.S.W)) · 2025Article
- Focus on cardiac troponin complex: From gene expression to cardiomyopathy.Genes & diseases · 2024Review
- Umbrella Sampling Simulations of Cardiac Thin Filament Reveal Thermodynamic Consequences of Troponin I Inhibitory Peptide Mutations.Journal of chemical information and modeling · 2023Article
- Human-Induced Pluripotent Stem Cell-Derived Cardiomyocyte Model forCirculation. Genomic and precision medicine · 2022Article
- Structure and Dynamics of the Flexible Cardiac Troponin T Linker Domain in a Fully Reconstituted Thin Filament.Biochemistry · 2022Article
- Thin filament cardiomyopathies: A review of genetics, disease mechanisms, and emerging therapeutics.Frontiers in cardiovascular medicine · 2022Review
- Cardiomyocyte Dysfunction in Inherited Cardiomyopathies.International journal of molecular sciences · 2021Review
- A Heterozygous Mutation in Cardiac Troponin T Promotes CaJournal of cardiovascular development and disease · 2021Article
- Cardiomyopathic troponin mutations predominantly occur at its interface with actin and tropomyosin.The Journal of general physiology · 2021Article
- Troponin Revealed: Uncovering the Structure of the Thin Filament On-Off Switch in Striated Muscle.Biophysical journal · 2021Review
- Troponin structure and function: a view of recent progress.Journal of muscle research and cell motility · 2020Review
- FRET-based analysis of the cardiac troponin T linker region reveals the structural basis of the hypertrophic cardiomyopathy-causing Δ160E mutation.The Journal of biological chemistry · 2019Article
- Moving beyond simple answers to complex disorders in sarcomeric cardiomyopathies: the role of integrated systems.Pflugers Archiv : European journal of physiology · 2019Review
- Computational Studies of Cardiac and Skeletal Troponin.Frontiers in molecular biosciences · 2019Review
- Mechanism of Cardiac Tropomyosin Transitions on Filamentous Actin As Revealed by All-Atom Steered Molecular Dynamics Simulations.The journal of physical chemistry letters · 2018Article
- Molecular mechanisms and structural features of cardiomyopathy-causing troponin T mutants in the tropomyosin overlap region.Proceedings of the National Academy of Sciences of the United States of America · 2017Article
- Pathogenesis of Hypertrophic Cardiomyopathy is Mutation Rather Than Disease Specific: A Comparison of the Cardiac Troponin T E163R and R92Q Mouse Models.Journal of the American Heart Association · 2017Article
- Atomic resolution probe for allostery in the regulatory thin filament.Proceedings of the National Academy of Sciences of the United States of America · 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
3 authors at 2 institutions in 1 country.
Funding
Abstract
Familial hypertrophic cardiomyopathy (FHC) is one of the most common genetic causes of heart disease. Approximately 15% of FHC-related mutations are found in cTnT [cardiac troponin (cTn) T]. Most of the cTnT FHC-related mutations are in or flanking the N-tail TNT1 domain that directly interacts with overlapping tropomyosin (Tm). We investigate two sets of cTnT mutations at opposite ends of TNT1, mutations in residue 92 in the Tm-Tm overlap region of TNT1 and mutations in residues 160 and 163 in the C-terminal portion of TNT1 adjacent to the cTnT H1-H2 linker. Though all the mutations are located within TNT1, they have widely different phenotypes clinically and biophysically. Using a complete atomistic model of the cTn-Tm complex, we identify mechanisms by which the effects of TNT1 mutations propagate to the cTn core and site II of cTnC, where calcium binding and dissociation occurs. We find that mutations in TNT1 alter the flexibility of TNT1, which is inversely proportional to the cooperativity of calcium activation of the thin filament. Further, we identify a pathway of propagation of structural and dynamic changes from TNT1 to site II of cTnC, including TNT1, cTnT linker, I-T arm, regulatory domain of cTnI, the D-E linker of cTnC, and site II cTnC. Mutationally induced changes at site II of cTnC alter calcium coordination that corresponds to biophysical measurements of calcium sensitivity. Finally, we compare this pathway of mutational propagation with that of the calcium activation of the thin filament and find that they are identical but opposite in direction.
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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.