ArticleThe Journal of biological chemistry2012
Structural dynamics of C-domain of cardiac troponin I protein in reconstituted thin filament.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 32 citations in OpenAlex.
- Myosin-actin crossbridge independent sarcomere length induced CaJournal of molecular and cellular cardiology · 2025Article
- Effects of cardiomyopathy-linked mutations K15N and R21H in tropomyosin on thin-filament regulation and pointed-end dynamics.Molecular biology of the cell · 2019Article
- CaBiophysical journal · 2018Article
- Role of the C-terminus mobile domain of cardiac troponin I in the regulation of thin filament activation in skinned papillary muscle strips.Archives of biochemistry and biophysics · 2018Article
- Functional significance of C-terminal mobile domain of cardiac troponin I.Archives of biochemistry and biophysics · 2017Article
- Dynamic Equilibrium of Cardiac Troponin C's Hydrophobic Cleft and Its Modulation by CaBioconjugate chemistry · 2017Article
- Heart Failure-Related Hyperphosphorylation in the Cardiac Troponin I C Terminus Has Divergent Effects on Cardiac Function In Vivo.Circulation. Heart failure · 2017Article
- Order-Disorder Transitions in the Cardiac Troponin Complex.Journal of molecular biology · 2016Review
- Sarcomere length dependent effects on the interaction between cTnC and cTnI in skinned papillary muscle strips.Archives of biochemistry and biophysics · 2016Article
- The functional significance of the last 5 residues of the C-terminus of cardiac troponin I.Archives of biochemistry and biophysics · 2016Article
- Role of cardiac troponin I carboxy terminal mobile domain and linker sequence in regulating cardiac contraction.Archives of biochemistry and biophysics · 2016Article
- Fluorescence Based Characterization of Calcium Sensitizer Action on the Troponin Complex.Chemical biology & drug design · 2016Article
- The Importance of Intrinsically Disordered Segments of Cardiac Troponin in Modulating Function by Phosphorylation and Disease-Causing Mutations.Frontiers in physiology · 2016Review
- Green Tea Catechin Normalizes the Enhanced Ca2+ Sensitivity of Myofilaments Regulated by a Hypertrophic Cardiomyopathy-Associated Mutation in Human Cardiac Troponin I (K206I).Circulation. Cardiovascular genetics · 2015Article
- Conformation and Dynamics of the Troponin I C-Terminal Domain: Combining Single-Molecule and Computational Approaches for a Disordered Protein Region.Journal of the American Chemical Society · 2015Article
- A novel phosphorylation site, Serine 199, in the C-terminus of cardiac troponin I regulates calcium sensitivity and susceptibility to calpain-induced proteolysis.Journal of molecular and cellular cardiology · 2015Article
- Mechanistic heterogeneity in contractile properties of α-tropomyosin (TPM1) mutants associated with inherited cardiomyopathies.The Journal of biological chemistry · 2015Article
- In situ time-resolved FRET reveals effects of sarcomere length on cardiac thin-filament activation.Biophysical journal · 2014Article
- FRET study of the structural and kinetic effects of PKC phosphomimetic cardiac troponin T mutants on thin filament regulation.Archives of biochemistry and biophysics · 2014Article
- Structural basis for the in situ Ca(2+) sensitization of cardiac troponin C by positive feedback from force-generating myosin cross-bridges.Archives of biochemistry and biophysics · 2013Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
The regulatory function of cardiac troponin I (cTnI) involves three important contiguous regions within its C-domain: the inhibitory region (IR), the regulatory region (RR), and the mobile domain (MD). Within these regions, the dynamics of regional structure and kinetics of transitions in dynamic state are believed to facilitate regulatory signaling. This study was designed to use fluorescence anisotropy techniques to acquire steady-state and kinetic information on the dynamic state of the C-domain of cTnI in the reconstituted thin filament. A series of single cysteine cTnI mutants was generated, labeled with the fluorophore tetramethylrhodamine, and subjected to various anisotropy experiments at the thin filament level. The structure of the IR was found to be less dynamic than that of the RR and the MD, and Ca(2+) binding induced minimal changes in IR dynamics: the flexibility of the RR decreased, whereas the MD became more flexible. Anisotropy stopped-flow experiments showed that the kinetics describing the transition of the MD and RR from the Ca(2+)-bound to the Ca(2+)-free dynamic states were significantly faster (53.2-116.8 s(-1)) than that of the IR (14.1 s(-1)). Our results support the fly casting mechanism, implying that an unstructured MD with rapid dynamics and kinetics plays a critical role to initiate relaxation upon Ca(2+) dissociation by rapidly interacting with actin to promote the dissociation of the RR from the N-domain of cTnC. In contrast, the IR responds to Ca(2+) signals with slow structural dynamics and transition kinetics. The collective findings suggested a fourth state of activation.
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