PDBsum entry 1spy

Go to PDB code: 
protein links
Muscle protein PDB id
Protein chain
89 a.a. *
* Residue conservation analysis
PDB id:
Name: Muscle protein
Title: Regulatory domain of human cardiac troponin c in the calcium-free state, nmr, 40 structures
Structure: Troponin c. Chain: a. Fragment: regulatory. Synonym: cntnc. Engineered: yes
Source: Homo sapiens. Human. Organism_taxid: 9606. Cell_line: bl21. Expressed in: escherichia coli. Expression_system_taxid: 562.
NMR struc: 40 models
Authors: L.Spyracopoulos,M.X.Li,S.K.Sia,S.M.Gagne,M.Chandra, R.J.Solaro,B.D.Sykes
Key ref:
L.Spyracopoulos et al. (1997). Calcium-induced structural transition in the regulatory domain of human cardiac troponin C. Biochemistry, 36, 12138-12146. PubMed id: 9315850 DOI: 10.1021/bi971223d
14-Jul-97     Release date:   16-Sep-98    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P63316  (TNNC1_HUMAN) -  Troponin C, slow skeletal and cardiac muscles
161 a.a.
89 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

 Gene Ontology (GO) functional annotation 
  GO annot!
  Biochemical function     calcium ion binding     1 term  


DOI no: 10.1021/bi971223d Biochemistry 36:12138-12146 (1997)
PubMed id: 9315850  
Calcium-induced structural transition in the regulatory domain of human cardiac troponin C.
L.Spyracopoulos, M.X.Li, S.K.Sia, S.M.Gagné, M.Chandra, R.J.Solaro, B.D.Sykes.
While calcium binding to troponin C (TnC) triggers the contraction of both skeletal and cardiac muscle, there is clear evidence that different mechanisms may be involved. For example, activation of heart myofilaments occurs with binding to a single regulatory site on TnC, whereas activation of fast skeletal myofilaments occurs with binding to two regulatory sites. The physiological difference between activation of cardiac and skeletal myofilaments is not understood at the molecular level due to a lack of structural details for the response of cardiac TnC to calcium. We determined the solution structures of the apo and calcium-saturated regulatory domain of human cardiac TnC by using multinuclear, multidimensional nuclear magnetic resonance spectroscopy. The structure of apo human cardiac TnC is very similar to that of apo turkey skeletal TnC even though there are critical amino acid substitutions in site I. In contrast to the case with the skeletal protein, the calcium-induced conformational transition in the cardiac regulatory domain does not involve an "opening" of the regulatory domain, and the concomitant exposure of a substantial hydrophobic surface area. This result has important implications with regard to potential unique aspects of the interaction of cardiac TnC with cardiac troponin I and of modification of cardiac myofilament regulation by calcium-sensitizer drugs.

Literature references that cite this PDB file's key reference

  PubMed id Reference
20128626 S.B.Tikunova, B.Liu, N.Swindle, S.C.Little, A.V.Gomes, D.R.Swartz, and J.P.Davis (2010).
Effect of calcium-sensitizing mutations on calcium binding and exchange with troponin C in increasingly complex biochemical systems.
  Biochemistry, 49, 1975-1984.  
19542563 I.M.Robertson, M.X.Li, and B.D.Sykes (2009).
Solution structure of human cardiac troponin C in complex with the green tea polyphenol, (-)-epigallocatechin 3-gallate.
  J Biol Chem, 284, 23012-23023.
PDB code: 2kdh
19419198 R.M.Hoffman, and B.D.Sykes (2009).
Structure of the inhibitor W7 bound to the regulatory domain of cardiac troponin C.
  Biochemistry, 48, 5541-5552.
PDB code: 2kfx
18212018 C.C.Lim, H.Yang, M.Yang, C.K.Wang, J.Shi, E.A.Berg, D.R.Pimentel, J.K.Gwathmey, R.J.Hajjar, M.Helmes, C.E.Costello, S.Huo, and R.Liao (2008).
A novel mutant cardiac troponin C disrupts molecular motions critical for calcium binding affinity and cardiomyocyte contractility.
  Biophys J, 94, 3577-3589.  
18280495 E.Johnson, L.Bruschweiler-Li, S.A.Showalter, G.W.Vuister, F.Zhang, and R.Brüschweiler (2008).
Structure and dynamics of Ca2+-binding domain 1 of the Na+/Ca2+ exchanger in the presence and in the absence of Ca2+.
  J Mol Biol, 377, 945-955.  
18570382 I.M.Robertson, O.K.Baryshnikova, M.X.Li, and B.D.Sykes (2008).
Defining the binding site of levosimendan and its analogues in a regulatory cardiac troponin C-troponin I complex.
  Biochemistry, 47, 7485-7495.  
18676638 J.M.Robinson, H.C.Cheung, and W.Dong (2008).
The cardiac Ca2+-sensitive regulatory switch, a system in dynamic equilibrium.
  Biophys J, 95, 4772-4789.  
18162171 M.X.Li, I.M.Robertson, and B.D.Sykes (2008).
Interaction of cardiac troponin with cardiotonic drugs: a structural perspective.
  Biochem Biophys Res Commun, 369, 88-99.  
18063575 W.J.Dong, J.Xing, Y.Ouyang, J.An, and H.C.Cheung (2008).
Structural kinetics of cardiac troponin C mutants linked to familial hypertrophic and dilated cardiomyopathy in troponin complexes.
  J Biol Chem, 283, 3424-3432.  
17180551 C.Eichmüller, and N.R.Skrynnikov (2007).
Observation of microsecond time-scale protein dynamics in the presence of Ln3+ ions: application to the N-terminal domain of cardiac troponin C.
  J Biomol NMR, 37, 79-95.  
17293397 J.P.Davis, C.Norman, T.Kobayashi, R.J.Solaro, D.R.Swartz, and S.B.Tikunova (2007).
Effects of thin and thick filament proteins on calcium binding and exchange with cardiac troponin C.
  Biophys J, 92, 3195-3206.  
16211482 C.Eichmüller, and N.R.Skrynnikov (2005).
A new amide proton R1rho experiment permits accurate characterization of microsecond time-scale conformational exchange.
  J Biomol NMR, 32, 281-293.  
15709952 T.Kobayashi, and R.J.Solaro (2005).
Calcium, thin filaments, and the integrative biology of cardiac contractility.
  Annu Rev Physiol, 67, 39-67.  
14978304 G.L.Gay, D.A.Lindhout, and B.D.Sykes (2004).
Using lanthanide ions to align troponin complexes in solution: order of lanthanide occupancy in cardiac troponin C.
  Protein Sci, 13, 640-651.  
15711886 M.X.Li, X.Wang, and B.D.Sykes (2004).
Structural based insights into the role of troponin in cardiac muscle pathophysiology.
  J Muscle Res Cell Motil, 25, 559-579.  
15205455 S.B.Tikunova, and J.P.Davis (2004).
Designing calcium-sensitizing mutations in the regulatory domain of cardiac troponin C.
  J Biol Chem, 279, 35341-35352.  
12732641 D.A.Lindhout, and B.D.Sykes (2003).
Structure and dynamics of the C-domain of human cardiac troponin C in complex with the inhibitory region of human cardiac troponin I.
  J Biol Chem, 278, 27024-27034.
PDB code: 1ozs
12920131 D.M.Casey, T.Yagi, R.Kamiya, and G.B.Witman (2003).
DC3, the smallest subunit of the Chlamydomonas flagellar outer dynein arm-docking complex, is a redox-sensitive calcium-binding protein.
  J Biol Chem, 278, 42652-42659.  
14661957 M.X.Li, X.Wang, D.A.Lindhout, N.Buscemi, J.E.Van Eyk, and B.D.Sykes (2003).
Phosphorylation and mutation of human cardiac troponin I deferentially destabilize the interaction of the functional regions of troponin I with troponin C.
  Biochemistry, 42, 14460-14468.  
12044157 D.A.Lindhout, M.X.Li, D.Schieve, and B.D.Sykes (2002).
Effects of T142 phosphorylation and mutation R145G on the interaction of the inhibitory region of human cardiac troponin I with the C-domain of human cardiac troponin C.
  Biochemistry, 41, 7267-7274.  
12060657 X.Wang, M.X.Li, and B.D.Sykes (2002).
Structure of the regulatory N-domain of human cardiac troponin C in complex with human cardiac troponin I147-163 and bepridil.
  J Biol Chem, 277, 31124-31133.
PDB code: 1lxf
11371454 D.A.Martyn, and A.M.Gordon (2001).
Influence of length on force and activation-dependent changes in troponin c structure in skinned cardiac and fast skeletal muscle.
  Biophys J, 80, 2798-2808.  
11159408 D.A.Martyn, M.Regnier, D.Xu, and A.M.Gordon (2001).
Ca2+ - and cross-bridge-dependent changes in N- and C-terminal structure of troponin C in rat cardiac muscle.
  Biophys J, 80, 360-370.  
11352734 M.B.Abbott, W.J.Dong, A.Dvoretsky, B.DaGue, R.M.Caprioli, H.C.Cheung, and P.R.Rosevear (2001).
Modulation of cardiac troponin C-cardiac troponin I regulatory interactions by the amino-terminus of cardiac troponin I.
  Biochemistry, 40, 5992-6001.  
11492964 Y.M.Liou (2001).
Effects of sarcomere length and Ca(2+) binding on h reactivity of myofilament bound troponin C in porcine skinned cardiac muscle fibers.
  Jpn J Physiol, 51, 385-388.  
11054120 K.Pääkkönen, T.Sorsa, T.Drakenberg, P.Pollesello, C.Tilgmann, P.Permi, S.Heikkinen, I.Kilpeläinen, and A.Annila (2000).
Conformations of the regulatory domain of cardiac troponin C examined by residual dipolar couplings.
  Eur J Biochem, 267, 6665-6672.  
10913289 M.X.Li, L.Spyracopoulos, N.Beier, J.A.Putkey, and B.D.Sykes (2000).
Interaction of cardiac troponin C with Ca(2+) sensitizer EMD 57033 and cardiac troponin I inhibitory peptide.
  Biochemistry, 39, 8782-8790.  
11090126 P.Kischel, B.Bastide, J.D.Potter, and Y.Mounier (2000).
The role of the Ca(2+) regulatory sites of skeletal troponin C in modulating muscle fibre reactivity to the Ca(2+) sensitizer bepridil.
  Br J Pharmacol, 131, 1496-1502.  
10715110 P.Mercier, M.X.Li, and B.D.Sykes (2000).
Role of the structural domain of troponin C in muscle regulation: NMR studies of Ca2+ binding and subsequent interactions with regions 1-40 and 96-115 of troponin I.
  Biochemistry, 39, 2902-2911.  
11027154 R.T.McKay, L.F.Saltibus, M.X.Li, and B.D.Sykes (2000).
Energetics of the induced structural change in a Ca2+ regulatory protein: Ca2+ and troponin I peptide binding to the E41A mutant of the N-domain of skeletal troponin C.
  Biochemistry, 39, 12731-12738.  
10792039 Y.Li, M.L.Love, J.A.Putkey, and C.Cohen (2000).
Bepridil opens the regulatory N-terminal lobe of cardiac troponin C.
  Proc Natl Acad Sci U S A, 97, 5140-5145.
PDB code: 1dtl
10439508 F.Wang, W.Li, M.R.Emmett, A.G.Marshall, D.Corson, and B.D.Sykes (1999).
Fourier transform ion cyclotron resonance mass spectrometric detection of small Ca(2+)-induced conformational changes in the regulatory domain of human cardiac troponin C.
  J Am Soc Mass Spectrom, 10, 703-710.  
10387077 G.M.Gasmi-Seabrook, J.W.Howarth, N.Finley, E.Abusamhadneh, V.Gaponenko, R.M.Brito, R.J.Solaro, and P.R.Rosevear (1999).
Solution structures of the C-terminal domain of cardiac troponin C free and bound to the N-terminal domain of cardiac troponin I.
  Biochemistry, 38, 8313-8322.
PDB codes: 1fi5 1ggs
10387074 M.X.Li, L.Spyracopoulos, and B.D.Sykes (1999).
Binding of cardiac troponin-I147-163 induces a structural opening in human cardiac troponin-C.
  Biochemistry, 38, 8289-8298.
PDB code: 1mxl
10516660 P.Kischel, L.Stevens, and Y.Mounier (1999).
Differential effects of bepridil on functional properties of troponin C in slow and fast skeletal muscles.
  Br J Pharmacol, 128, 767-773.  
10446160 Q.Kleerekoper, and J.A.Putkey (1999).
Drug binding to cardiac troponin C.
  J Biol Chem, 274, 23932-23939.  
10220335 R.T.McKay, B.P.Tripet, J.R.Pearlstone, L.B.Smillie, and B.D.Sykes (1999).
Defining the region of troponin-I that binds to troponin-C.
  Biochemistry, 38, 5478-5489.  
10231519 S.Tsuda, A.Miura, S.M.Gagné, L.Spyracopoulos, and B.D.Sykes (1999).
Low-temperature-induced structural changes in the Apo regulatory domain of skeletal muscle troponin C.
  Biochemistry, 38, 5693-5700.
PDB codes: 1skt 1zac
10531339 W.J.Dong, J.Xing, M.Villain, M.Hellinger, J.M.Robinson, M.Chandra, R.J.Solaro, P.K.Umeda, and H.C.Cheung (1999).
Conformation of the regulatory domain of cardiac muscle troponin C in its complex with cardiac troponin I.
  J Biol Chem, 274, 31382-31390.  
9667926 J.Evenäs, A.Malmendal, and S.Forsén (1998).
  Curr Opin Chem Biol, 2, 293-302.  
9624156 K.Pääkkönen, A.Annila, T.Sorsa, P.Pollesello, C.Tilgmann, I.Kilpeläinen, P.Karisola, I.Ulmanen, and T.Drakenberg (1998).
Solution structure and main chain dynamics of the regulatory domain (Residues 1-91) of human cardiac troponin C.
  J Biol Chem, 273, 15633-15638.  
9922172 L.Spyracopoulos, S.M.Gagné, M.X.Li, and B.D.Sykes (1998).
Dynamics and thermodynamics of the regulatory domain of human cardiac troponin C in the apo- and calcium-saturated states.
  Biochemistry, 37, 18032-18044.  
9525919 Q.Kleerekoper, W.Liu, D.Choi, and J.A.Putkey (1998).
Identification of binding sites for bepridil and trifluoperazine on cardiac troponin C.
  J Biol Chem, 273, 8153-8160.  
9585577 R.R.Biekofsky, S.R.Martin, J.P.Browne, P.M.Bayley, and J.Feeney (1998).
Ca2+ coordination to backbone carbonyl oxygen atoms in calmodulin and other EF-hand proteins: 15N chemical shifts as probes for monitoring individual-site Ca2+ coordination.
  Biochemistry, 37, 7617-7629.  
9730814 R.T.McKay, J.R.Pearlstone, D.C.Corson, S.M.Gagné, L.B.Smillie, and B.D.Sykes (1998).
Structure and interaction site of the regulatory domain of troponin-C when complexed with the 96-148 region of troponin-I.
  Biochemistry, 37, 12419-12430.
PDB code: 1blq
The most recent references are shown first. Citation data come partly from CiteXplore and partly from an automated harvesting procedure. Note that this is likely to be only a partial list as not all journals are covered by either method. However, we are continually building up the citation data so more and more references will be included with time. Where a reference describes a PDB structure, the PDB code is shown on the right.