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Structure and dynamics of the C-domain of human cardiac troponin C in complex with the inhibitory region of human cardiac troponin I.

Lindhout DA, Sykes BD
J Biol Chem 278 27024-34 (2003)
Cited: 30 times
EuropePMC logo PMID: 12732641

Abstract

Cardiac troponin C is the Ca2+-dependent switch for heart muscle contraction. Troponin C is associated with various other proteins including troponin I and troponin T. The interaction between the subunits within the troponin complex is of critical importance in understanding contractility. Following a Ca2+ signal to begin contraction, the inhibitory region of troponin I comprising residues Thr128-Arg147 relocates from its binding surface on actin to troponin C, triggering movement of troponin-tropomyosin within the thin filament and thereby freeing actin-binding site(s) for interactions with the myosin ATPase of the thick filament to generate the power stroke. The structure of calcium-saturated cardiac troponin C (C-domain) in complex with the inhibitory region of troponin I was determined using multinuclear and multidimensional nuclear magnetic resonance spectroscopy. The structure of this complex reveals that the inhibitory region adopts a helical conformation spanning residues Leu134-Lys139, with a novel orientation between the E- and H-helices of troponin C, which is largely stabilized by electrostatic interactions. By using isotope labeling, we have studied the dynamics of the protein and peptide in the binary complex. The structure of this inhibited complex provides a framework for understanding into interactions within the troponin complex upon heart contraction.

Reviews - 1ozs mentioned but not cited (1)

  1. Structure and function of cardiac troponin C (TNNC1): Implications for heart failure, cardiomyopathies, and troponin modulating drugs. Li MX, Hwang PM. Gene 571 153-166 (2015)

Articles - 1ozs mentioned but not cited (3)

  1. Characterization of calumenin-SERCA2 interaction in mouse cardiac sarcoplasmic reticulum. Sahoo SK, Kim T, Kang GB, Lee JG, Eom SH, Kim DH. J Biol Chem 284 31109-31121 (2009)
  2. The role of electrostatics in the interaction of the inhibitory region of troponin I with troponin C. Lindhout DA, Boyko RF, Corson DC, Li MX, Sykes BD. Biochemistry 44 14750-14759 (2005)
  3. Familial Dilated Cardiomyopathy Associated With a Novel Combination of Compound Heterozygous TNNC1 Variants. Landim-Vieira M, Johnston JR, Ji W, Mis EK, Tijerino J, Spencer-Manzon M, Jeffries L, Hall EK, Panisello-Manterola D, Khokha MK, Deniz E, Chase PB, Lakhani SA, Pinto JR. Front Physiol 10 1612 (2019)


Reviews citing this publication (11)

  1. Calcium, thin filaments, and the integrative biology of cardiac contractility. Kobayashi T, Solaro RJ. Annu Rev Physiol 67 39-67 (2005)
  2. Sarcomeric proteins and familial hypertrophic cardiomyopathy: linking mutations in structural proteins to complex cardiovascular phenotypes. Tardiff JC. Heart Fail Rev 10 237-248 (2005)
  3. Covalent and noncovalent modification of thin filament action: the essential role of troponin in cardiac muscle regulation. Metzger JM, Westfall MV. Circ Res 94 146-158 (2004)
  4. Structural based insights into the role of troponin in cardiac muscle pathophysiology. Li MX, Wang X, Sykes BD. J Muscle Res Cell Motil 25 559-579 (2004)
  5. The contractile apparatus as a target for drugs against heart failure: interaction of levosimendan, a calcium sensitiser, with cardiac troponin c. Sorsa T, Pollesello P, Solaro RJ. Mol Cell Biochem 266 87-107 (2004)
  6. Interaction of cardiac troponin with cardiotonic drugs: a structural perspective. Li MX, Robertson IM, Sykes BD. Biochem Biophys Res Commun 369 88-99 (2008)
  7. Cardiac troponin structure-function and the influence of hypertrophic cardiomyopathy associated mutations on modulation of contractility. Cheng Y, Regnier M. Arch Biochem Biophys 601 11-21 (2016)
  8. Cardiac Troponin and Tropomyosin: Structural and Cellular Perspectives to Unveil the Hypertrophic Cardiomyopathy Phenotype. Marques MA, de Oliveira GA. Front Physiol 7 429 (2016)
  9. Through thick and thin: dual regulation of insect flight muscle and cardiac muscle compared. Bullard B, Pastore A. J Muscle Res Cell Motil 40 99-110 (2019)
  10. The missing links within troponin. Marques MA, Parvatiyar MS, Yang W, de Oliveira GAP, Pinto JR. Arch Biochem Biophys 663 95-100 (2019)
  11. Calcium Handling in Inherited Cardiac Diseases: A Focus on Catecholaminergic Polymorphic Ventricular Tachycardia and Hypertrophic Cardiomyopathy. Zaffran S, Kraoua L, Jaouadi H. Int J Mol Sci 24 3365 (2023)

Articles citing this publication (15)

  1. Genetic polymorphism and protein conformational plasticity in the calmodulin superfamily: two ways to promote multifunctionality. Ikura M, Ames JB. Proc Natl Acad Sci U S A 103 1159-1164 (2006)
  2. Internal pH indicators for biomolecular NMR. Baryshnikova OK, Williams TC, Sykes BD. J Biomol NMR 41 5-7 (2008)
  3. Solution structure of human cardiac troponin C in complex with the green tea polyphenol, (-)-epigallocatechin 3-gallate. Robertson IM, Li MX, Sykes BD. J Biol Chem 284 23012-23023 (2009)
  4. Structure of trans-resveratrol in complex with the cardiac regulatory protein troponin C. Pineda-Sanabria SE, Robertson IM, Sykes BD. Biochemistry 50 1309-1320 (2011)
  5. Calcium-dependent changes in the flexibility of the regulatory domain of troponin C in the troponin complex. Blumenschein TM, Stone DB, Fletterick RJ, Mendelson RA, Sykes BD. J Biol Chem 280 21924-21932 (2005)
  6. News Pulling the calcium trigger. Sykes BD. Nat Struct Biol 10 588-589 (2003)
  7. Novel frameshift mutation in Troponin C ( TNNC1) associated with hypertrophic cardiomyopathy and sudden death. Chung WK, Kitner C, Maron BJ. Cardiol Young 21 345-348 (2011)
  8. Defining the binding site of levosimendan and its analogues in a regulatory cardiac troponin C-troponin I complex. Robertson IM, Baryshnikova OK, Li MX, Sykes BD. Biochemistry 47 7485-7495 (2008)
  9. Single histidine button in cardiac troponin I sustains heart performance in response to severe hypercapnic respiratory acidosis in vivo. Palpant NJ, D'Alecy LG, Metzger JM. FASEB J 23 1529-1540 (2009)
  10. The structure of Lethocerus troponin C: insights into the mechanism of stretch activation in muscles. De Nicola G, Burkart C, Qiu F, Agianian B, Labeit S, Martin S, Bullard B, Pastore A. Structure 15 813-824 (2007)
  11. Ca2+-induced PRE-NMR changes in the troponin complex reveal the possessive nature of the cardiac isoform for its regulatory switch. Cordina NM, Liew CK, Potluri PR, Curmi PM, Fajer PG, Logan TM, Mackay JP, Brown LJ. PLoS One 9 e112976 (2014)
  12. Determination of the 19F NMR chemical shielding tensor and crystal structure of 5-fluoro-dl-tryptophan. Zhao X, DeVries JS, McDonald R, Sykes BD. J Magn Reson 187 88-96 (2007)
  13. Proof of Principle that Molecular Modeling Followed by a Biophysical Experiment Can Develop Small Molecules that Restore Function to the Cardiac Thin Filament in the Presence of Cardiomyopathic Mutations. Szatkowski L, Lynn ML, Holeman T, Williams MR, Baldo AP, Tardiff JC, Schwartz SD. ACS Omega 4 6492-6501 (2019)
  14. Letter '(De-)sensitization' vs. 'Uncoupling': what drives cardiomyopathies in the thin filament? Hwang PM. Cardiovasc Res 109 185-186 (2016)
  15. Structure and dynamics of endogenous cardiac troponin complex in human heart tissue captured by native nanoproteomics. Chapman EA, Roberts DS, Tiambeng TN, Andrews J, Wang MD, Reasoner EA, Melby JA, Li BH, Kim D, Alpert AJ, Jin S, Ge Y. Nat Commun 14 8400 (2023)


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