troponin c

Summary

Summary: A TROPONIN complex subunit that binds calcium and help regulate calcium-dependent muscle contraction. There are two troponin C subtypes: troponin C1 and C2. Troponin C1 is skeletal and cardiac type whereas troponin C2 is skeletal type. Troponin C1 is a BIOMARKER for damaged or injured CARDIAC MYOCYTES and mutations in troponin C1 gene are associated with FAMILIAL HYPERTROPHIC CARDIOMYOPATHY.

Top Publications

  1. Dong W, Xing J, Ouyang Y, An J, Cheung H. Structural kinetics of cardiac troponin C mutants linked to familial hypertrophic and dilated cardiomyopathy in troponin complexes. J Biol Chem. 2008;283:3424-32 pubmed
    The key events in regulating cardiac muscle contraction involve Ca(2+) binding to and release from cTnC (troponin C) and structural changes in cTnC and other thin filament proteins triggered by Ca(2+) movement...
  2. Kobayashi T, Jin L, de Tombe P. Cardiac thin filament regulation. Pflugers Arch. 2008;457:37-46 pubmed publisher
    ..Here, we review current knowledge regarding protein-protein interactions involved in the dynamics of thin filament activation and relaxation and the regulation of these processes by protein kinase-mediated phosphorylation. ..
  3. Jeong K, Kim C, Un S, Yi M, Lee I, Park J, et al. Allergenicity of recombinant troponin C from Tyrophagus putrescentiae. Int Arch Allergy Immunol. 2010;151:207-13 pubmed publisher
    ..This study was undertaken to characterize the allergenicity of troponin C from T. putrescentiae. A cDNA encoding 17...
  4. Liou Y, Chang J. Differential pH effect on calcium-induced conformational changes of cardiac troponin C complexed with cardiac and fast skeletal isoforms of troponin I and troponin T. J Biochem. 2004;136:683-92 pubmed
    ..of the effects of increasing acidity on the Ca(2+) induced conformational changes of pyrene labelled cardiac troponin C (PIA-cTnC) in isolation and in complex with porcine cardiac or chicken pectoral skeletal muscle TnI and/or TnT...
  5. Moreno Gonzalez A, Fredlund J, Regnier M. Cardiac troponin C (TnC) and a site I skeletal TnC mutant alter Ca2+ versus crossbridge contribution to force in rabbit skeletal fibres. J Physiol. 2005;562:873-84 pubmed
    We studied the relative contributions of Ca(2+) binding to troponin C (TnC) and myosin binding to actin in activating thin filaments of rabbit psoas fibres...
  6. Herranz R, Mateos J, Marco R. Diversification and independent evolution of troponin C genes in insects. J Mol Evol. 2005;60:31-44 pubmed publisher
    b>Troponin C (TpnC), the calcium-binding subunit of the troponin regulatory complex in the muscle thin filament, is encoded by multiple genes in insects...
  7. Blumenschein T, Stone D, Fletterick R, Mendelson R, Sykes B. Calcium-dependent changes in the flexibility of the regulatory domain of troponin C in the troponin complex. J Biol Chem. 2005;280:21924-32 pubmed
    ..We used NMR techniques to study the backbone dynamics of skeletal troponin C (TnC) in the complex...
  8. Ramos C, Lima M, Silva S, Borin P, Regis W, Santoro M. Stability and folding studies of the N-domain of troponin C. Evidence for the formation of an intermediate. Arch Biochem Biophys. 2004;427:135-42 pubmed
    ..on the stability and folding of the 91 residue alpha-helical F29W N-terminal domain of chicken skeletal muscle troponin C (TnC(1-91)F29W), the thin filament calcium-binding component...
  9. Du C, Morimoto S, Nishii K, Minakami R, Ohta M, Tadano N, et al. Knock-in mouse model of dilated cardiomyopathy caused by troponin mutation. Circ Res. 2007;101:185-94 pubmed

More Information

Publications62

  1. Gillis T, Tibbits G. Beating the cold: the functional evolution of troponin C in teleost fish. Comp Biochem Physiol A Mol Integr Physiol. 2002;132:763-72 pubmed
    ..myocyte is due, at least in part, to changes in the amino acid sequence of the thin filament protein, cardiac troponin C (cTnC). cTnC is the Ca(2+)-activated switch that triggers myocyte contraction...
  2. Knowles A, Irving M, Sun Y. Conformation of the troponin core complex in the thin filaments of skeletal muscle during relaxation and active contraction. J Mol Biol. 2012;421:125-37 pubmed publisher
    ..Here, we use polarized fluorescence to determine the orientation of the C-terminal lobe of troponin C (TnC) in skeletal muscle cells as a step toward elucidating the molecular mechanism of troponin-mediated ..
  3. Martyn D, Gordon A. Influence of length on force and activation-dependent changes in troponin c structure in skinned cardiac and fast skeletal muscle. Biophys J. 2001;80:2798-808 pubmed
    ..dichroism of 5' tetramethyl-rhodamine (5'ATR) was measured to monitor the effect of sarcomere length (SL) on troponin C (TnC) structure during Ca2+ activation in single glycerinated rabbit psoas fibers and skinned right ventricular ..
  4. Morris C, Tobacman L, Homsher E. Modulation of contractile activation in skeletal muscle by a calcium-insensitive troponin C mutant. J Biol Chem. 2001;276:20245-51 pubmed
    ..Replacement of the native, skeletal calcium-binding subunit of troponin, troponin C, with mixtures of functional cardiac and mutant cardiac troponin C insensitive to calcium and permanently ..
  5. Chandra M, Kim J, Solaro R. An improved method for exchanging troponin subunits in detergent skinned rat cardiac fiber bundles. Biochem Biophys Res Commun. 1999;263:219-23 pubmed
    ..Complete reconstitution of the Tn complex was achieved by reconstituting with cardiac troponin C (cTnC) in fully relaxing conditions...
  6. Lee R, Tikunova S, Kline K, Zot H, Hasbun J, Minh N, et al. Effect of Ca2+ binding properties of troponin C on rate of skeletal muscle force redevelopment. Am J Physiol Cell Physiol. 2010;299:C1091-9 pubmed publisher
    ..Thus TnC mutants with altered Ca(2+) binding properties can control the rate of contraction by modulating thin filament activation without directly affecting intrinsic cross-bridge cycling rates...
  7. Rieck D, Li K, Ouyang Y, Solaro R, Dong W. Structural basis for the in situ Ca(2+) sensitization of cardiac troponin C by positive feedback from force-generating myosin cross-bridges. Arch Biochem Biophys. 2013;537:198-209 pubmed publisher
  8. Neulen A, Stehle R, Pfitzer G. The cardiac troponin C mutation Leu29Gln found in a patient with hypertrophic cardiomyopathy does not alter contractile parameters in skinned murine myocardium. Basic Res Cardiol. 2009;104:751-60 pubmed publisher
    The present study investigates the effects of the first mutation of troponin C (hcTnC(L29Q)) found in a patient with hypertrophic cardiomyopathy (HCM) on force-pCa relations and the interplay with phosphorylation of sarcomeric PKA ..
  9. Liu B, Tikunova S, Kline K, Siddiqui J, Davis J. Disease-related cardiac troponins alter thin filament Ca2+ association and dissociation rates. PLoS ONE. 2012;7:e38259 pubmed publisher
    ..By utilizing an IAANS labeled fluorescent troponin C, [Formula: see text], we examined the effects of ten disease-related troponin modifications on the Ca(2+) ..
  10. Cordina N, Liew C, Gell D, Fajer P, Mackay J, Brown L. Interdomain orientation of cardiac troponin C characterized by paramagnetic relaxation enhancement NMR reveals a compact state. Protein Sci. 2012;21:1376-87 pubmed publisher
    Cardiac troponin C (cTnC) is the calcium binding subunit of the troponin complex that triggers the thin filament response to calcium influx into the sarcomere...
  11. Gillis T, Marshall C, Tibbits G. Functional and evolutionary relationships of troponin C. Physiol Genomics. 2007;32:16-27 pubmed
    ..is initiated when, following membrane depolarization, Ca(2+) binds to the low-affinity Ca(2+) binding sites of troponin C (TnC)...
  12. Parvatiyar M, Landstrom A, Figueiredo Freitas C, Potter J, Ackerman M, Pinto J. A mutation in TNNC1-encoded cardiac troponin C, TNNC1-A31S, predisposes to hypertrophic cardiomyopathy and ventricular fibrillation. J Biol Chem. 2012;287:31845-55 pubmed publisher
    ..Mutations in TNNC1-encoded cardiac troponin C (cTnC) are a relatively rare cause of HCM...
  13. Biesiadecki B, Kobayashi T, Walker J, Solaro R, de Tombe P. The troponin C G159D mutation blunts myofilament desensitization induced by troponin I Ser23/24 phosphorylation. Circ Res. 2007;100:1486-93 pubmed
    ..Striated muscle contraction is regulated by the binding of Ca(2+) to the N-terminal regulatory lobe of the cardiac troponin C (cTnC) subunit in the troponin complex...
  14. Hindley J, Wunschmann S, Satinover S, Woodfolk J, Chew F, Chapman M, et al. Bla g 6: a troponin C allergen from Blattella germanica with IgE binding calcium dependence. J Allergy Clin Immunol. 2006;117:1389-95 pubmed
    ..Three isoallergens of troponin C (Bla g 6) were cloned and expressed in Pichia pastoris. Homology modeling was performed by using Swiss-Model...
  15. Lindert S, Kekenes Huskey P, McCammon J. Long-timescale molecular dynamics simulations elucidate the dynamics and kinetics of exposure of the hydrophobic patch in troponin C. Biophys J. 2012;103:1784-9 pubmed publisher
    ..Calcium binding to the troponin C (TnC) subunit causes a change in its dynamics that leads to the transient opening of a hydrophobic patch on TnC'..
  16. Terami H, Williams B, Kitamura S, Sakube Y, Matsumoto S, Doi S, et al. Genomic organization, expression, and analysis of the troponin C gene pat-10 of Caenorhabditis elegans. J Cell Biol. 1999;146:193-202 pubmed
    We have cloned and characterized the troponin C gene, pat-10 of the nematode Caenorhabditis elegans...
  17. Ferguson R, Sun Y, Mercier P, Brack A, Sykes B, Corrie J, et al. In situ orientations of protein domains: troponin C in skeletal muscle fibers. Mol Cell. 2003;11:865-74 pubmed
    ..Polarized fluorescence from bifunctional rhodamine probes attached along four alpha helices of troponin C (TnC) was measured in permeabilized skeletal muscle fibers...
  18. Spyracopoulos L, Lavigne P, Crump M, Gagné S, Kay C, Sykes B. Temperature dependence of dynamics and thermodynamics of the regulatory domain of human cardiac troponin C. Biochemistry. 2001;40:12541-51 pubmed
    Binding of Ca(2+) to the regulatory domain of troponin C (TnC) in cardiac muscle initiates a series of protein conformational changes and modified protein-protein interactions that initiate contraction...
  19. Newman E, Spratt D, Mosher J, Cheyne B, Montgomery H, Wilson D, et al. Differential activation of nitric-oxide synthase isozymes by calmodulin-troponin C chimeras. J Biol Chem. 2004;279:33547-57 pubmed
    ..of neuronal nitric-oxide synthase (nNOS) with calmodulin (CaM) and mutant forms of CaM, including CaM-troponin C chimeras, have been previously reported, but there has been no comparable investigation of CaM interactions with ..
  20. de Paula Brotto M, van Leyen S, Brotto L, Jin J, Nosek C, Nosek T. Hypoxia/fatigue-induced degradation of troponin I and troponin C: new insights into physiologic muscle fatigue. Pflugers Arch. 2001;442:738-44 pubmed
  21. Agianian B, Krzic U, Qiu F, Linke W, Leonard K, Bullard B. A troponin switch that regulates muscle contraction by stretch instead of calcium. EMBO J. 2004;23:772-9 pubmed
  22. Wang X, Li M, Spyracopoulos L, Beier N, Chandra M, Solaro R, et al. Structure of the C-domain of human cardiac troponin C in complex with the Ca2+ sensitizing drug EMD 57033. J Biol Chem. 2001;276:25456-66 pubmed
    Ca(2+) binding to cardiac troponin C (cTnC) triggers contraction in heart muscle...
  23. Daubert M, Jeremias A. The utility of troponin measurement to detect myocardial infarction: review of the current findings. Vasc Health Risk Manag. 2010;6:691-9 pubmed
    ..This review describes the role of troponin in the evaluation of patients with suspected myocardial infarction. ..
  24. Kreutziger K, Piroddi N, McMichael J, Tesi C, Poggesi C, Regnier M. Calcium binding kinetics of troponin C strongly modulate cooperative activation and tension kinetics in cardiac muscle. J Mol Cell Cardiol. 2011;50:165-74 pubmed publisher
    ..development and relaxation in cardiac muscle are regulated at the thin filament via Ca(2+) binding to cardiac troponin C (cTnC) and strong cross-bridge binding...
  25. Grabarek Z. Insights into modulation of calcium signaling by magnesium in calmodulin, troponin C and related EF-hand proteins. Biochim Biophys Acta. 2011;1813:913-21 pubmed publisher
    ..This article is part of a Special Issue entitled: 11th European Symposium on Calcium. ..
  26. Dupuis L, Mousseau N. Understanding the EF-hand closing pathway using non-biased interatomic potentials. J Chem Phys. 2012;136:035101 pubmed publisher
    ..pathway, from the unbound holo state to the closed apo state, of two EF-hand proteins, the Calmodulin and Troponin C N-terminal nodules...
  27. Adhikari B, Wang K. Interplay of troponin- and Myosin-based pathways of calcium activation in skeletal and cardiac muscle: the use of W7 as an inhibitor of thin filament activation. Biophys J. 2004;86:359-70 pubmed
    ..in striated muscle, we employed n-(6-aminohexyl) 5-chloro-1-napthalenesulfonamide (W7) as an inhibitor of troponin C and compared its effects with that of the myosin-specific inhibitor, 2,3-butanedione 2-monoxime (BDM)...
  28. Howarth J, Meller J, Solaro R, Trewhella J, Rosevear P. Phosphorylation-dependent conformational transition of the cardiac specific N-extension of troponin I in cardiac troponin. J Mol Biol. 2007;373:706-22 pubmed
    ..In this conformation, TnI(1-32) interacts with the N-lobe of cardiac troponin C (cTnC) and thus is positioned to modulate myofilament Ca2+-sensitivity...
  29. Katayama K, Tomatsu M, Kawahara S, Yamauchi K, Fuchu H, Kodama Y, et al. Inhibitory profile of nonapeptide derived from porcine troponin C against angiotensin I-converting enzyme. J Agric Food Chem. 2004;52:771-5 pubmed
    A novel angiotensin I-converting enzyme (ACE) inhibitory peptide (RMLGQTPTK; 9mer) from porcine skeletal troponin C was investigated for its inhibitory profile...
  30. Liou Y, Chao H. Fluorescence spectroscopic analysis of the proximity changes between the central helix of troponin C and the C-terminus of troponin T from chicken skeletal muscle. Biochim Biophys Acta. 2007;1774:466-73 pubmed
    ..These results suggest that TnI plays an essential role in the Ca(2+) -mediated change in the spatial relationship between the C-lobe of TnC and the C-terminus of TnT. ..
  31. Blumenschein T, Stone D, Fletterick R, Mendelson R, Sykes B. Dynamics of the C-terminal region of TnI in the troponin complex in solution. Biophys J. 2006;90:2436-44 pubmed
  32. Mirza M, Marston S, Willott R, Ashley C, Mogensen J, McKenna W, et al. Dilated cardiomyopathy mutations in three thin filament regulatory proteins result in a common functional phenotype. J Biol Chem. 2005;280:28498-506 pubmed
    ..Inherited DCM can result from mutations in the genes encoding cardiac troponin T, troponin C, and alpha-tropomyosin; different mutations in the same genes cause hypertrophic cardiomyopathy...
  33. Tikunova S, Davis J. Designing calcium-sensitizing mutations in the regulatory domain of cardiac troponin C. J Biol Chem. 2004;279:35341-52 pubmed
    Cardiac troponin C belongs to the EF-hand superfamily of calcium-binding proteins and plays an essential role in the regulation of muscle contraction and relaxation...
  34. Little S, Biesiadecki B, Kilic A, Higgins R, Janssen P, Davis J. The rates of Ca2+ dissociation and cross-bridge detachment from ventricular myofibrils as reported by a fluorescent cardiac troponin C. J Biol Chem. 2012;287:27930-40 pubmed publisher
    ..Both the rates of cross-bridge detachment and Ca(2+) dissociation from troponin C (TnC) have been hypothesized to rate-limit myofilament inactivation...
  35. Hoffmann B, Schmidt Traub H, Perrot A, Osterziel K, Gessner R. First mutation in cardiac troponin C, L29Q, in a patient with hypertrophic cardiomyopathy. Hum Mutat. 2001;17:524 pubmed
  36. Digel J, Abugo O, Kobayashi T, Gryczynski Z, Lakowicz J, Collins J. Calcium- and magnesium-dependent interactions between the C-terminus of troponin I and the N-terminal, regulatory domain of troponin C. Arch Biochem Biophys. 2001;387:243-9 pubmed
    ..b>Troponin C (TnC), the Ca2+ binding subunit of Tn contains two homologous domains and four divalent cation binding sites...
  37. Landstrom A, Parvatiyar M, Pinto J, Marquardt M, Bos J, Tester D, et al. Molecular and functional characterization of novel hypertrophic cardiomyopathy susceptibility mutations in TNNC1-encoded troponin C. J Mol Cell Cardiol. 2008;45:281-8 pubmed publisher
    ..Many of these mutations appear to affect the functional properties of cardiac troponin C (cTnC), i.e...
  38. Arteaga G, Kobayashi T, Solaro R. Molecular actions of drugs that sensitize cardiac myofilaments to Ca2+. Ann Med. 2002;34:248-58 pubmed
    ..We focus here on Ca(2+)-sensitizers that act on cardiac troponin C, the Ca2+ receptor that triggers activation of the actin-myosin interaction...
  39. Heller W, Abusamhadneh E, Finley N, Rosevear P, Trewhella J. The solution structure of a cardiac troponin C-troponin I-troponin T complex shows a somewhat compact troponin C interacting with an extended troponin I-troponin T component. Biochemistry. 2002;41:15654-63 pubmed
    ..A., and Trewhella, J. (1994) Biochemistry 33, 12800-12806]. ..
  40. Sorsa T, Pollesello P, Solaro R. The contractile apparatus as a target for drugs against heart failure: interaction of levosimendan, a calcium sensitiser, with cardiac troponin c. Mol Cell Biochem. 2004;266:87-107 pubmed
    ..Levosimendan is a novel calcium sensitiser which has been discovered by using cardiac troponin C (cTnC) as target protein...
  41. Liang B, Chung F, Qu Y, Pavlov D, Gillis T, Tikunova S, et al. Familial hypertrophic cardiomyopathy-related cardiac troponin C mutation L29Q affects Ca2+ binding and myofilament contractility. Physiol Genomics. 2008;33:257-66 pubmed publisher
    The cardiac troponin C (cTnC) mutation, L29Q, has been found in a patient with familial hypertrophic cardiomyopathy...
  42. Burkart E, Arteaga G, Sumandea M, Prabhakar R, Wieczorek D, Solaro R. Altered signaling surrounding the C-lobe of cardiac troponin C in myofilaments containing an alpha-tropomyosin mutation linked to familial hypertrophic cardiomyopathy. J Mol Cell Cardiol. 2003;35:1285-93 pubmed
    A region of interaction between the near N-terminal of cardiac troponin I (cTnI) and the C-lobe of troponin C (cTnC), where troponin T (cTnT) binds, appears to be critical in regulation of myofilament Ca(2+)-activation...
  43. Dong W, Jayasundar J, An J, Xing J, Cheung H. Effects of PKA phosphorylation of cardiac troponin I and strong crossbridge on conformational transitions of the N-domain of cardiac troponin C in regulated thin filaments. Biochemistry. 2007;46:9752-61 pubmed
    Regulation of cardiac muscle function is initiated by binding of Ca2+ to troponin C (cTnC) which induces a series of structural changes in cTnC and other thin filament proteins...
  44. Schmidtmann A, Lindow C, Villard S, Heuser A, Mugge A, Gessner R, et al. Cardiac troponin C-L29Q, related to hypertrophic cardiomyopathy, hinders the transduction of the protein kinase A dependent phosphorylation signal from cardiac troponin I to C. FEBS J. 2005;272:6087-97 pubmed
    ..The findings imply a hindered transduction of the phosphorylation signal from cTnI to cTnC. ..
  45. Finley N, Rosevear P. Introduction of negative charge mimicking protein kinase C phosphorylation of cardiac troponin I. Effects on cardiac troponin C. J Biol Chem. 2004;279:54833-40 pubmed
    ..In this work, NMR was used to identify conformational and dynamic changes in cardiac troponin C upon binding a phosphomimetic troponin I, having Ser(43)/Ser(45) mutated to Asp...
  46. Dweck D, Reynaldo D, Pinto J, Potter J. A dilated cardiomyopathy troponin C mutation lowers contractile force by reducing strong myosin-actin binding. J Biol Chem. 2010;285:17371-9 pubmed publisher
    In this study we explore the mechanisms by which a double mutation (E59D/D75Y) in cardiac troponin C (CTnC) associated with dilated cardiomyopathy reduces the Ca(2+)-activated maximal tension of cardiac muscle...
  47. Varughese J, Chalovich J, Li Y. Molecular dynamics studies on troponin (TnI-TnT-TnC) complexes: insight into the regulation of muscle contraction. J Biomol Struct Dyn. 2010;28:159-74 pubmed
    ..This approach may give insight into the mechanism by which mutations of troponin cause disease. It is interesting that some observed disease causing mutations fall within regions of troponin that are strongly correlated or interacted. ..
  48. Tikunova S, Liu B, Swindle N, Little S, Gomes A, Swartz D, et al. Effect of calcium-sensitizing mutations on calcium binding and exchange with troponin C in increasingly complex biochemical systems. Biochemistry. 2010;49:1975-84 pubmed publisher
    The calcium-dependent interactions between troponin C (TnC) and other thin and thick filament proteins play a key role in the regulation of cardiac muscle contraction...
  49. Takeda S, Yamashita A, Maeda K, Maeda Y. Structure of the core domain of human cardiac troponin in the Ca(2+)-saturated form. Nature. 2003;424:35-41 pubmed
  50. Wang X, Li M, Sykes B. Structure of the regulatory N-domain of human cardiac troponin C in complex with human cardiac troponin I147-163 and bepridil. J Biol Chem. 2002;277:31124-33 pubmed
    Cardiac troponin C (cTnC) is the Ca(2+)-dependent switch for contraction in heart muscle and a potential target for drugs in the therapy of heart failure...
  51. Davis J, Norman C, Kobayashi T, Solaro R, Swartz D, Tikunova S. Effects of thin and thick filament proteins on calcium binding and exchange with cardiac troponin C. Biophys J. 2007;92:3195-206 pubmed
    Understanding the effects of thin and thick filament proteins on the kinetics of Ca(2+) exchange with cardiac troponin C is essential to elucidating the Ca(2+)-dependent mechanisms controlling cardiac muscle contraction and relaxation...
  52. Lindhout D, Boyko R, Corson D, Li M, Sykes B. The role of electrostatics in the interaction of the inhibitory region of troponin I with troponin C. Biochemistry. 2005;44:14750-9 pubmed
    ..the electrostatic interactions occurring between the inhibitory region of cardiac troponin I with the C-lobe of troponin C using scanning glycine mutagenesis of the inhibitory region...
  53. Cordina N, Liew C, Gell D, Fajer P, Mackay J, Brown L. Effects of calcium binding and the hypertrophic cardiomyopathy A8V mutation on the dynamic equilibrium between closed and open conformations of the regulatory N-domain of isolated cardiac troponin C. Biochemistry. 2013;52:1950-62 pubmed publisher
    b>Troponin C (TnC) is the calcium-binding subunit of the troponin complex responsible for initiating striated muscle contraction in response to calcium influx...