ArticleBiochemistry2017
Clinically Divergent Mutation Effects on the Structure and Function of the Human Cardiac Tropomyosin Overlap.
Article in Biochemistry, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
26 citing papers in PubMed, 28 citations in OpenAlex.
- Resolving the structure and dynamics of the disordered C terminus of human cardiac troponin T and effects of cardiomyopathic mutations.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Screening single nucleotide changes to tropomyosin to identify novel cardiomyopathy mutants.Journal of molecular and cellular cardiology · 2025Article
- Modeling the effects of thin filament near-neighbor cooperative interactions in mammalian myocardium.The Journal of general physiology · 2025Article
- Dilated Cardiomyopathy - Exploring the Underlying Causes.Medical research archives · 2024Article
- Arg92Leu-cTnT Alters the cTnC-cTnI Interface Disrupting PKA-Mediated Relaxation.Circulation research · 2024Article
- Mechanisms of Sarcomere Protein Mutation-Induced Cardiomyopathies.Current cardiology reports · 2023Review
- 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
- Computational and biophysical determination of pathogenicity of variants of unknown significance in cardiac thin filament.JCI insight · 2021Article
- A troponin T variant linked with pediatric dilated cardiomyopathy reduces the coupling of thin filament activation to myosin and calcium binding.Molecular biology of the cell · 2021Article
- Mechanical dysfunction of the sarcomere induced by a pathogenic mutation in troponin T drives cellular adaptation.The Journal of general physiology · 2021Article
- Cardiomyopathic troponin mutations predominantly occur at its interface with actin and tropomyosin.The Journal of general physiology · 2021Article
- Complexity in genetic cardiomyopathies and new approaches for mechanism-based precision medicine.The Journal of general physiology · 2021Article
- A high-throughput fluorescence lifetime-based assay to detect binding of myosin-binding protein C to F-actin.The Journal of general physiology · 2021Article
- Modulating the tension-time integral of the cardiac twitch prevents dilated cardiomyopathy in murine hearts.JCI insight · 2020Article
- Review
- Thin filament dysfunctions caused by mutations in tropomyosin Tpm3.12 and Tpm1.1.Journal of muscle research and cell motility · 2020Review
- A new twist on tropomyosin binding to actin filaments: perspectives on thin filament function, assembly and biomechanics.Journal of muscle research and cell motility · 2020Review
- A Stochastic Multiscale Model of Cardiac Thin Filament Activation Using Brownian-Langevin Dynamics.Biophysical journal · 2019Article
- Combinatorial genetic replenishments in myocardial and outflow tract tissues restore heart function inBiology open · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
The progression of genetically inherited cardiomyopathies from an altered protein structure to clinical presentation of disease is not well understood. One of the main roadblocks to mechanistic insight remains a lack of high-resolution structural information about multiprotein complexes within the cardiac sarcomere. One example is the tropomyosin (Tm) overlap region of the thin filament that is crucial for the function of the cardiac sarcomere. To address this central question, we devised coupled experimental and computational modalities to characterize the baseline function and structure of the Tm overlap, as well as the effects of mutations causing divergent patterns of ventricular remodeling on both structure and function. Because the Tm overlap contributes to the cooperativity of myofilament activation, we hypothesized that mutations that enhance the interactions between overlap proteins result in more cooperativity, and conversely, those that weaken interaction between these elements lower cooperativity. Our results suggest that the Tm overlap region is affected differentially by dilated cardiomyopathy-associated Tm D230N and hypertrophic cardiomyopathy-associated human cardiac troponin T (cTnT) R92L. The Tm D230N mutation compacts the Tm overlap region, increasing the cooperativity of the Tm filament, contributing to a dilated cardiomyopathy phenotype. The cTnT R92L mutation causes weakened interactions closer to the N-terminal end of the overlap, resulting in decreased cooperativity. These studies demonstrate that mutations with differential phenotypes exert opposite effects on the Tm-Tn overlap, and that these effects can be directly correlated to a molecular level understanding of the structure and dynamics of the component proteins.
Indexed as
Identifiers
What OpenQuestion holds
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.