ArticleFrontiers in physiology2016
Myofilament Calcium Sensitivity: Consequences of the Effective Concentration of Troponin I.
Article in Frontiers in physiology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 45 citations in OpenAlex.
- GSK3β-driven phosphorylation of ABLIM1 regulates its interactions with titin cardiac muscle.The Journal of general physiology · 2025Article
- Dual role of Tropomyosin-R160 in thin filament regulation: Insights into phosphorylation-dependent cardiac relaxation and cardiomyopathy mechanisms.Archives of biochemistry and biophysics · 2025Article
- Arg92Leu-cTnT Alters the cTnC-cTnI Interface Disrupting PKA-Mediated Relaxation.Circulation research · 2024Article
- Substrate mechanics unveil early structural and functional pathology in iPSC micro-tissue models of hypertrophic cardiomyopathy.iScience · 2024Article
- Troponin Structural Dynamics in the Native Cardiac Thin Filament Revealed by Cryo Electron Microscopy.Journal of molecular biology · 2024Article
- Glutamate 139 of tropomyosin is critical for cardiac thin filament blocked-state stabilization.Journal of molecular and cellular cardiology · 2024Article
- Mouse Models of Cardiomyopathies Caused by Mutations in Troponin C.International journal of molecular sciences · 2023Review
- Targeting Troponin C with Small Molecules Containing Diphenyl Moieties: Calcium Sensitivity Effects on Striated Muscles and Structure-Activity Relationship.Journal of chemical information and modeling · 2023Article
- Umbrella Sampling Simulations of Cardiac Thin Filament Reveal Thermodynamic Consequences of Troponin I Inhibitory Peptide Mutations.Journal of chemical information and modeling · 2023Article
- Machine learning meets Monte Carlo methods for models of muscle's molecular machinery to classify mutations.The Journal of general physiology · 2023Article
- The lack of Troponin I Ser-23/24 phosphorylation is detrimental to in vivo cardiac function and exacerbates cardiac disease.Journal of molecular and cellular cardiology · 2023Article
- Targeting Troponin C with Small Molecules Containing Diphenyl Moieties: Calcium Sensitivity Effects on Striated Muscle and Structure Activity Relationship.bioRxiv : the preprint server for biology · 2023Article
- Myofilament-associated proteins with intrinsic disorder (MAPIDs) and their resolution by computational modeling.Quarterly reviews of biophysics · 2023Review
- Multiscale simulation-guided design of enzyme bioconjugates with enhanced catalysis.Chem catalysis · 2022Article
- Article
- Small Molecule RPI-194 Stabilizes Activated Troponin to Increase the Calcium Sensitivity of Striated Muscle Contraction.Frontiers in physiology · 2022Article
- Negative inotropic mechanisms of β-cardiotoxin in cardiomyocytes by depression of myofilament ATPase activity without activation of the classical β-adrenergic pathway.Scientific reports · 2021Article
- Computational Methods Elucidate Consequences of Mutations and Post-translational Modifications on Troponin I Effective Concentration to Troponin C.The journal of physical chemistry. B · 2021Article
- Cardiomyopathic troponin mutations predominantly occur at its interface with actin and tropomyosin.The Journal of general physiology · 2021Article
- Discovery of Novel Small-Molecule Calcium Sensitizers for Cardiac Troponin C: A Combined Virtual and Experimental Screening Approach.Journal of chemical information and modeling · 2020Article
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 1 country.
Funding
Abstract
Control of calcium binding to and dissociation from cardiac troponin C (TnC) is essential to healthy cardiac muscle contraction/relaxation. There are numerous aberrant post-translational modifications and mutations within a plethora of contractile, and even non-contractile, proteins that appear to imbalance this delicate relationship. The direction and extent of the resulting change in calcium sensitivity is thought to drive the heart toward one type of disease or another. There are a number of molecular mechanisms that may be responsible for the altered calcium binding properties of TnC, potentially the most significant being the ability of the regulatory domain of TnC to bind the switch peptide region of TnI. Considering TnI is essentially tethered to TnC and cannot diffuse away in the absence of calcium, we suggest that the apparent calcium binding properties of TnC are highly dependent upon an "effective concentration" of TnI available to bind TnC. Based on our previous work, TnI peptide binding studies and the calcium binding properties of chimeric TnC-TnI fusion constructs, and building upon the concept of effective concentration, we have developed a mathematical model that can simulate the steady-state and kinetic calcium binding properties of a wide assortment of disease-related and post-translational protein modifications in the isolated troponin complex and reconstituted thin filament. We predict that several TnI and TnT modifications do not alter any of the intrinsic calcium or TnI binding constants of TnC, but rather alter the ability of TnC to "find" TnI in the presence of calcium. These studies demonstrate the apparent consequences of the effective TnI concentration in modulating the calcium binding properties of TnC.
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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.