PDBsum entry 1tnx

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Calcium-binding protein PDB id
Protein chain
145 a.a. *
* Residue conservation analysis
PDB id:
Name: Calcium-binding protein
Title: Nmr solution structure of calcium saturated skeletal muscle troponin c
Structure: Troponin c. Chain: a. Engineered: yes. Mutation: yes
Source: Gallus gallus. Chicken. Organism_taxid: 9031. Organ: skeletal. Tissue: skeletal muscle. Expressed in: escherichia coli. Expression_system_taxid: 562.
NMR struc: 1 models
Authors: C.M.Slupsky,B.D.Sykes
Key ref:
C.M.Slupsky and B.D.Sykes (1995). NMR solution structure of calcium-saturated skeletal muscle troponin C. Biochemistry, 34, 15953-15964. PubMed id: 8519752
23-Aug-95     Release date:   15-Oct-95    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P02588  (TNNC2_CHICK) -  Troponin C, skeletal muscle
163 a.a.
145 a.a.*
Key:    PfamA domain  Secondary structure  CATH domain
* PDB and UniProt seqs differ at 1 residue position (black cross)

 Gene Ontology (GO) functional annotation 
  GO annot!
  Cellular component     troponin complex   1 term 
  Biological process     skeletal muscle contraction   1 term 
  Biochemical function     actin binding     3 terms  


Biochemistry 34:15953-15964 (1995)
PubMed id: 8519752  
NMR solution structure of calcium-saturated skeletal muscle troponin C.
C.M.Slupsky, B.D.Sykes.
Troponin C (TnC) is an 18 kDa (162-residue) thin-filament calcium-binding protein responsible for triggering muscle contraction upon the release of calcium from the sarcoplasmic reticulum. The structure of TnC with two calcium ions bound has previously been solved by X-ray methods. Shown here is the solution structure of TnC which has been solved using 3D and 4D heteronuclear nuclear magnetic resonance (NMR) spectroscopic techniques. The 1H, 13C, and 15N backbone chemical shifts have already been published [Slupsky, C. M., Reinach, F. C., Smillie, L. B., & Sykes, B. D. (1995) Protein Sci. 4, 1279-1290]. Presented herein are the 1H, 13C, and 15N side-chain chemical shifts which are 80% complete. The structure of calcium-saturated TnC was determined on the basis of 2106 NOE-derived distance restraints, 121 phi dihedral angle restraints, and 76 psi dihedral angle restraints. The appearance of calcium-saturated TnC reveals a dumbbell-shaped molecule with two globular domains connected by a linker. The structures of the N-terminal and C-terminal domains are highly converged [backbone atomic root mean square deviations (rmsd) about the mean atomic coordinate position for residues 10-80 and 98-155 are 0.66 +/- 0.17 and 0.69 +/- 0.18 A, respectively]; however, the orientation of one domain with respect to the other is not well-defined, and thus each domain appears to be structurally independent. Comparison of the calcium-saturated form of TnC determined herein with the half-saturated form determined by X-ray methods reveals two major differences. First, there is a major structural change which occurs in the N-terminal domain resulting in the opening of a hydrophobic pocket presumably to present itself to its target protein troponin I. This structural change appears to involve only helices B and C which move away from helices N/A/D by the alteration of the backbone phi, psi angles of glutamic acid 41 from irregular in the crystal structure (-97 degrees, -7 degrees) to helical in the NMR calcium-saturated structure (-60 degrees, -34 degrees). The other difference between the two structures is the presence of a flexible linker between the two domains in the NMR structure. This flexible linker allows the two domains of TnC to adopt any orientation with respect to one another such that they can interact with a variety of targets.

Literature references that cite this PDB file's key reference

  PubMed id Reference
21262274 Z.Grabarek (2011).
Insights into modulation of calcium signaling by magnesium in calmodulin, troponin C and related EF-hand proteins.
  Biochim Biophys Acta, 1813, 913-921.  
20053351 Tombe, R.D.Mateja, K.Tachampa, Y.Ait Mou, G.P.Farman, and T.C.Irving (2010).
Myofilament length dependent activation.
  J Mol Cell Cardiol, 48, 851-858.  
19289050 M.C.Mathur, T.Kobayashi, and J.M.Chalovich (2009).
Some cardiomyopathy-causing troponin I mutations stabilize a functional intermediate actin state.
  Biophys J, 96, 2237-2244.  
19472326 O.Julien, P.Mercier, M.L.Crane, and B.D.Sykes (2009).
The effect of the cosolvent trifluoroethanol on a tryptophan side chain orientation in the hydrophobic core of troponin C.
  Protein Sci, 18, 1165-1174.
PDB code: 2kgb
17872964 M.C.Mathur, T.Kobayashi, and J.M.Chalovich (2008).
Negative charges at protein kinase C sites of troponin I stabilize the inactive state of actin.
  Biophys J, 94, 542-549.  
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.  
17391016 H.Xie, S.Vucetic, L.M.Iakoucheva, C.J.Oldfield, A.K.Dunker, Z.Obradovic, and V.N.Uversky (2007).
Functional anthology of intrinsic disorder. 3. Ligands, post-translational modifications, and diseases associated with intrinsically disordered proteins.
  J Proteome Res, 6, 1917-1932.  
17519025 S.C.Flores, L.J.Lu, J.Yang, N.Carriero, and M.B.Gerstein (2007).
Hinge Atlas: relating protein sequence to sites of structural flexibility.
  BMC Bioinformatics, 8, 167.  
16957918 F.Capozzi, F.Casadei, and C.Luchinat (2006).
EF-hand protein dynamics and evolution of calcium signal transduction: an NMR view.
  J Biol Inorg Chem, 11, 949-962.  
16531415 T.Kobayashi, and R.J.Solaro (2006).
Increased Ca2+ affinity of cardiac thin filaments reconstituted with cardiomyopathy-related mutant cardiac troponin I.
  J Biol Chem, 281, 13471-13477.  
15784741 M.V.Vinogradova, D.B.Stone, G.G.Malanina, C.Karatzaferi, R.Cooke, R.A.Mendelson, and R.J.Fletterick (2005).
Ca(2+)-regulated structural changes in troponin.
  Proc Natl Acad Sci U S A, 102, 5038-5043.
PDB codes: 1ytz 1yv0
16416043 P.VanBuren, and Y.Okada (2005).
Thin filament remodeling in failing myocardium.
  Heart Fail Rev, 10, 199-209.  
15709952 T.Kobayashi, and R.J.Solaro (2005).
Calcium, thin filaments, and the integrative biology of cardiac contractility.
  Annu Rev Physiol, 67, 39-67.  
15826946 T.M.Blumenschein, D.B.Stone, R.J.Fletterick, R.A.Mendelson, and B.D.Sykes (2005).
Calcium-dependent changes in the flexibility of the regulatory domain of troponin C in the troponin complex.
  J Biol Chem, 280, 21924-21932.  
15155727 A.M.Weljie, and H.J.Vogel (2004).
Unexpected structure of the Ca2+-regulatory region from soybean calcium-dependent protein kinase-alpha.
  J Biol Chem, 279, 35494-35502.
PDB code: 1s6i
14765112 B.Agianian, U.Krzic, F.Qiu, W.A.Linke, K.Leonard, and B.Bullard (2004).
A troponin switch that regulates muscle contraction by stretch instead of calcium.
  EMBO J, 23, 772-779.  
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.  
14970231 J.P.Davis, J.A.Rall, C.Alionte, and S.B.Tikunova (2004).
Mutations of hydrophobic residues in the N-terminal domain of troponin C affect calcium binding and exchange with the troponin C-troponin I96-148 complex and muscle force production.
  J Biol Chem, 279, 17348-17360.  
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.  
12886291 B.D.Sykes (2003).
Pulling the calcium trigger.
  Nat Struct Biol, 10, 588-589.  
12557238 B.Tripet, G.De Crescenzo, S.Grothe, M.O'Connor-McCourt, and R.S.Hodges (2003).
Kinetic analysis of the interactions between troponin C (TnC) and troponin I (TnI) binding peptides: evidence for separate binding sites for the 'structural' N-terminus and the 'regulatory' C-terminus of TnI on TnC.
  J Mol Recognit, 16, 37-53.  
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
12531902 F.F.Valencia, A.A.Paulucci, R.B.Quaggio, A.C.Da Silva, C.S.Farah, and F.C.Reinach (2003).
Parallel measurement of Ca2+ binding and fluorescence emission upon Ca2+ titration of recombinant skeletal muscle troponin C. Measurement of sequential calcium binding to the regulatory sites.
  J Biol Chem, 278, 11007-11014.  
12524267 F.Pitici (2003).
Structural preference for changes in the direction of the Ca2+-induced transition: a study of the regulatory domain of skeletal troponin-C.
  Biophys J, 84, 82.  
12709056 G.Nicastro, L.Franzoni, Chiara, A.C.Mancin, J.R.Giglio, and A.Spisni (2003).
Solution structure of crotamine, a Na+ channel affecting toxin from Crotalus durissus terrificus venom.
  Eur J Biochem, 270, 1969-1979.
PDB code: 1h5o
12493841 M.Palczewska, P.Groves, G.Batta, B.Heise, and J.Ku┼║nicki (2003).
Calretinin and calbindin D28k have different domain organizations.
  Protein Sci, 12, 180-184.  
12475978 R.Maytum, B.Westerdorf, K.Jaquet, and M.A.Geeves (2003).
Differential regulation of the actomyosin interaction by skeletal and cardiac troponin isoforms.
  J Biol Chem, 278, 6696-6701.  
12840750 S.Takeda, A.Yamashita, K.Maeda, and Y.Maéda (2003).
Structure of the core domain of human cardiac troponin in the Ca(2+)-saturated form.
  Nature, 424, 35-41.
PDB codes: 1j1d 1j1e
12709434 V.Raussens, C.M.Slupsky, B.D.Sykes, and R.O.Ryan (2003).
Lipid-bound structure of an apolipoprotein E-derived peptide.
  J Biol Chem, 278, 25998-26006.  
12022873 S.B.Tikunova, J.A.Rall, and J.P.Davis (2002).
Effect of hydrophobic residue substitutions with glutamine on Ca(2+) binding and exchange with the N-domain of troponin C.
  Biochemistry, 41, 6697-6705.  
12036962 V.Raussens, C.M.Slupsky, R.O.Ryan, and B.D.Sykes (2002).
NMR structure and dynamics of a receptor-active apolipoprotein E peptide.
  J Biol Chem, 277, 29172-29180.  
11266616 A.Ababou, and J.R.Desjarlais (2001).
Solvation energetics and conformational change in EF-hand proteins.
  Protein Sci, 10, 301-312.  
11423417 Z.Li, J.Gergely, and T.Tao (2001).
Proximity relationships between residue 117 of rabbit skeletal troponin-I and residues in troponin-C and actin.
  Biophys J, 81, 321-333.  
  10933496 C.S.Tung, M.E.Wall, S.C.Gallagher, and J.Trewhella (2000).
A model of troponin-I in complex with troponin-C using hybrid experimental data: the inhibitory region is a beta-hairpin.
  Protein Sci, 9, 1312-1326.
PDB code: 1ew7
11076523 D.J.Black, S.B.Tikunova, J.D.Johnson, and J.P.Davis (2000).
Acid pairs increase the N-terminal Ca2+ affinity of CaM by increasing the rate of Ca2+ association.
  Biochemistry, 39, 13831-13837.  
10747786 J.K.Krueger, S.C.Gallagher, C.A.Wang, and J.Trewhella (2000).
Calmodulin remains extended upon binding to smooth muscle caldesmon: a combined small-angle scattering and fourier transform infrared spectroscopy study.
  Biochemistry, 39, 3979-3987.  
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.  
  10933493 N.D.Kurniawan, A.R.Atkins, S.Bieri, C.J.Brown, I.M.Brereton, P.A.Kroon, and R.Smith (2000).
NMR structure of a concatemer of the first and second ligand-binding modules of the human low-density lipoprotein receptor.
  Protein Sci, 9, 1282-1293.
PDB code: 1f5y
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.  
10625482 T.Kobayashi, M.Kobayashi, Z.Gryczynski, J.R.Lakowicz, and J.H.Collins (2000).
Inhibitory region of troponin I: Ca(2+)-dependent structural and environmental changes in the troponin-tropomyosin complex and in reconstituted thin filaments.
  Biochemistry, 39, 86-91.  
11112516 Y.Luo, J.Leszyk, B.Li, J.Gergely, and T.Tao (2000).
Proximity relationships between residue 6 of troponin I and residues in troponin C: further evidence for extended conformation of troponin C in the troponin complex.
  Biochemistry, 39, 15306-15315.  
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.  
10651267 J.Soman, T.Tao, and G.N.Phillips (1999).
Conformational variation of calcium-bound troponin C.
  Proteins, 37, 510-511.
PDB code: 1tcf
9876151 L.Smith, N.J.Greenfield, and S.E.Hitchcock-DeGregori (1999).
Mutations in the N- and D-helices of the N-domain of troponin C affect the C-domain and regulatory function.
  Biophys J, 76, 400-408.  
10364176 M.C.Moncrieffe, S.Eaton, Z.Bajzer, C.Haydock, J.D.Potter, T.M.Laue, and F.G.Prendergast (1999).
Rotational and translational motion of troponin C.
  J Biol Chem, 274, 17464-17470.  
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
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.  
10574794 S.Rothemund, Y.C.Liou, P.L.Davies, E.Krause, and F.D.Sönnichsen (1999).
A new class of hexahelical insect proteins revealed as putative carriers of small hydrophobic ligands.
  Structure, 7, 1325-1332.
PDB codes: 1c3y 1c3z
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
10220325 T.Kobayashi, X.Zhao, R.Wade, and J.H.Collins (1999).
Involvement of conserved, acidic residues in the N-terminal domain of troponin C in calcium-dependent regulation.
  Biochemistry, 38, 5386-5391.  
10082949 T.Kobayashi, X.Zhao, R.Wade, and J.H.Collins (1999).
Ca2+-dependent interaction of the inhibitory region of troponin I with acidic residues in the N-terminal domain of troponin C.
  Biochim Biophys Acta, 1430, 214-221.  
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.  
9770451 C.M.Slupsky, L.N.Gentile, L.W.Donaldson, C.D.Mackereth, J.J.Seidel, B.J.Graves, and L.P.McIntosh (1998).
Structure of the Ets-1 pointed domain and mitogen-activated protein kinase phosphorylation site.
  Proc Natl Acad Sci U S A, 95, 12129-12134.
PDB code: 1bqv
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.  
  9521102 M.R.Nelson, and W.J.Chazin (1998).
An interaction-based analysis of calcium-induced conformational changes in Ca2+ sensor proteins.
  Protein Sci, 7, 270-282.  
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
9519411 S.P.Smith, and G.S.Shaw (1998).
A novel calcium-sensitive switch revealed by the structure of human S100B in the calcium-bound form.
  Structure, 6, 211-222.
PDB code: 1uwo
9635764 Y.Luo, J.L.Wu, J.Gergely, and T.Tao (1998).
Localization of Cys133 of rabbit skeletal troponin-I with respect to troponin-C by resonance energy transfer.
  Biophys J, 74, 3111-3119.  
9199794 D.R.Swartz, R.L.Moss, and M.L.Greaser (1997).
Characteristics of troponin C binding to the myofibrillar thin filament: extraction of troponin C is not random along the length of the thin filament.
  Biophys J, 73, 293-305.  
9476523 H.C.Li, K.Hideg, and P.G.Fajer (1997).
The mobility of troponin C and troponin I in muscle.
  J Mol Recognit, 10, 194-201.  
9200712 J.R.Pearlstone, B.D.Sykes, and L.B.Smillie (1997).
Interactions of structural C and regulatory N domains of troponin C with repeated sequence motifs in troponin I.
  Biochemistry, 36, 7601-7606.  
  9416612 L.A.Kelley, and M.J.Sutcliffe (1997).
OLDERADO: on-line database of ensemble representatives and domains. On Line Database of Ensemble Representatives And DOmains.
  Protein Sci, 6, 2628-2630.  
9315850 L.Spyracopoulos, M.X.Li, S.K.Sia, S.M.Gagné, M.Chandra, R.J.Solaro, and B.D.Sykes (1997).
Calcium-induced structural transition in the regulatory domain of human cardiac troponin C.
  Biochemistry, 36, 12138-12146.
PDB codes: 1ap4 1spy
9353310 R.T.McKay, B.P.Tripet, R.S.Hodges, and B.D.Sykes (1997).
Interaction of the second binding region of troponin I with the regulatory domain of skeletal muscle troponin C as determined by NMR spectroscopy.
  J Biol Chem, 272, 28494-28500.  
9218458 S.K.Sia, M.X.Li, L.Spyracopoulos, S.M.Gagné, W.Liu, J.A.Putkey, and B.D.Sykes (1997).
Structure of cardiac muscle troponin C unexpectedly reveals a closed regulatory domain.
  J Biol Chem, 272, 18216-18221.
PDB codes: 1aj4 2ctn 3ctn
9109645 S.M.Gagné, M.X.Li, and B.D.Sykes (1997).
Mechanism of direct coupling between binding and induced structural change in regulatory calcium binding proteins.
  Biochemistry, 36, 4386-4392.
PDB code: 1smg
9219516 S.Takeda, T.Kobayashi, H.Taniguchi, H.Hayashi, and Y.Maéda (1997).
Structural and functional domains of the troponin complex revealed by limited digestion.
  Eur J Biochem, 246, 611-617.  
9283095 Y.Luo, J.L.Wu, J.Gergely, and T.Tao (1997).
Troponin T and Ca2+ dependence of the distance between Cys48 and Cys133 of troponin I in the ternary troponin complex and reconstituted thin filaments.
  Biochemistry, 36, 11027-11035.  
  9098903 Y.Saijo, S.Takeda, A.Scherer, T.Kobayashi, Y.Maéda, H.Taniguchi, M.Yao, and S.Wakatsuki (1997).
Production, crystallization, and preliminary X-ray analysis of rabbit skeletal muscle troponin complex consisting of troponin C and fragment (1-47) of troponin I.
  Protein Sci, 6, 916-918.  
8672464 E.J.Beatty, M.C.Cox, T.A.Frenkiel, B.M.Tam, A.B.Mason, R.T.MacGillivray, P.J.Sadler, and R.C.Woodworth (1996).
Interlobe communication in 13C-methionine-labeled human transferrin.
  Biochemistry, 35, 7635-7642.  
8652520 G.S.Shaw, and B.D.Sykes (1996).
NMR solution structure of a synthetic troponin C heterodimeric domain.
  Biochemistry, 35, 7429-7438.
PDB code: 1pon
8909299 R.S.Fredricksen, and C.A.Swenson (1996).
Relationship between stability and function for isolated domains of troponin C.
  Biochemistry, 35, 14012-14026.  
8952505 S.Ramakrishnan, and S.E.Hitchcock-DeGregori (1996).
Structural and functional significance of aspartic acid 89 of the troponin C central helix in Ca2+ signaling.
  Biochemistry, 35, 15515-15521.  
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.