PDBsum entry 1tnq

Go to PDB code: 
protein metals links
Calcium-binding protein PDB id
Protein chain
90 a.a. *
_CA ×2
* Residue conservation analysis
PDB id:
Name: Calcium-binding protein
Title: Structures of the apo and calcium troponin-c regulatory domains: the muscle contraction switch
Structure: Troponin-c. Chain: a. Synonym: ntnc apo. Engineered: yes
Source: Gallus gallus. Chicken. Organism_taxid: 9031. Tissue: skeleton. Gene: ntnc. Expressed in: escherichia coli. Expression_system_taxid: 562.
NMR struc: 40 models
Authors: S.M.Gagne,B.D.Sykes
Key ref: S.M.Gagné et al. (1995). Structures of the troponin C regulatory domains in the apo and calcium-saturated states. Nat Struct Biol, 2, 784-789. PubMed id: 7552750
07-Jul-95     Release date:   15-Oct-95    
Go to PROCHECK summary

Protein chain
Pfam   ArchSchema ?
P02588  (TNNC2_CHICK) -  Troponin C, skeletal muscle
163 a.a.
90 a.a.
Key:    PfamA domain  Secondary structure  CATH domain

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


Nat Struct Biol 2:784-789 (1995)
PubMed id: 7552750  
Structures of the troponin C regulatory domains in the apo and calcium-saturated states.
S.M.Gagné, S.Tsuda, M.X.Li, L.B.Smillie, B.D.Sykes.
Regulation of contraction in skeletal muscle occurs through calcium binding to the protein troponin C. The solution structures of the regulatory domain of apo and calcium-loaded troponin C have been determined by multinuclear, multidimensional nuclear magnetic resonance techniques. The structural transition in the regulatory domain of troponin C on calcium binding involves an opening of the structure through large changes in interhelical angles. This leads to the increased exposure of an extensive hydrophobic patch, an event that triggers skeletal muscle contraction.

Literature references that cite this PDB file's key reference

  PubMed id Reference
21269277 L.Santamaria-Kisiel, and G.S.Shaw (2011).
Identification of regions responsible for the open conformation of S100A10 using chimaeric S100A11-S100A10 proteins.
  Biochem J, 434, 37-48.  
20116385 M.Oleszczuk, I.M.Robertson, M.X.Li, and B.D.Sykes (2010).
Solution structure of the regulatory domain of human cardiac troponin C in complex with the switch region of cardiac troponin I and W7: the basis of W7 as an inhibitor of cardiac muscle contraction.
  J Mol Cell Cardiol, 48, 925-933.
PDB code: 2krd
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.  
19518255 A.M.Alencar, J.P.Butler, and S.M.Mijailovich (2009).
Thermodynamic origin of cooperativity in actomyosin interactions: the coupling of short-range interactions with actin bending stiffness in an Ising-like model.
  Phys Rev E Stat Nonlin Soft Matter Phys, 79, 041906.  
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
18942727 J.L.Li, C.Y.Geng, Y.Bu, X.R.Huang, and C.C.Sun (2009).
Conformational transition pathway in the allosteric process of calcium-induced recoverin: molecular dynamics simulations.
  J Comput Chem, 30, 1135-1145.  
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
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
18942859 D.S.Pearson, D.R.Swartz, and M.A.Geeves (2008).
Fast pressure jumps can perturb calcium and magnesium binding to troponin C F29W.
  Biochemistry, 47, 12146-12158.  
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.  
18559337 J.N.Wingard, J.Ladner, M.Vanarotti, A.J.Fisher, H.Robinson, K.T.Buchanan, D.M.Engman, and J.B.Ames (2008).
Structural Insights into Membrane Targeting by the Flagellar Calcium-binding Protein (FCaBP), a Myristoylated and Palmitoylated Calcium Sensor in Trypanosoma cruzi.
  J Biol Chem, 283, 23388-23396.
PDB code: 3cs1
18689462 M.C.Suarez, C.B.Rocha, M.M.Sorenson, J.L.Silva, and D.Foguel (2008).
Free-energy linkage between folding and calcium binding in EF-hand proteins.
  Biophys J, 95, 4820-4828.  
17994617 M.M.Ribeiro, H.G.Franquelim, M.A.Castanho, and A.S.Veiga (2008).
Molecular interaction studies of peptides using steady-state fluorescence intensity. Static (de)quenching revisited.
  J Pept Sci, 14, 401-406.  
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.  
18384084 S.Malik, M.Revington, S.P.Smith, and G.S.Shaw (2008).
Analysis of the structure of human apo-S100B at low temperature indicates a unimodal conformational distribution is adopted by calcium-free S100 proteins.
  Proteins, 73, 28-42.
PDB code: 2pru
18602402 T.H.Charpentier, P.T.Wilder, M.A.Liriano, K.M.Varney, E.Pozharski, A.D.MacKerell, A.Coop, E.A.Toth, and D.J.Weber (2008).
Divalent metal ion complexes of S100B in the absence and presence of pentamidine.
  J Mol Biol, 382, 56-73.
PDB codes: 3cr2 3cr4 3cr5
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.  
17101992 Y.B.Sun, B.Brandmeier, and M.Irving (2006).
Structural changes in troponin in response to Ca2+ and myosin binding to thin filaments during activation of skeletal muscle.
  Proc Natl Acad Sci U S A, 103, 17771-17776.  
15670158 A.O.Tiroli, L.Tasic, C.L.Oliveira, C.Bloch, I.Torriani, C.S.Farah, and C.H.Ramos (2005).
Mapping contacts between regulatory domains of skeletal muscle TnC and TnI by analyses of single-chain chimeras.
  FEBS J, 272, 779-790.  
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.  
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.  
14982937 B.Bánfi, F.Tirone, I.Durussel, J.Knisz, P.Moskwa, G.Z.Molnár, K.H.Krause, and J.A.Cox (2004).
Mechanism of Ca2+ activation of the NADPH oxidase 5 (NOX5).
  J Biol Chem, 279, 18583-18591.  
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.  
14980206 W.Zhou, Y.Qian, K.Kunjilwar, P.J.Pfaffinger, and S.Choe (2004).
Structural insights into the functional interaction of KChIP1 with Shal-type K(+) channels.
  Neuron, 41, 573-586.
PDB code: 1s6c
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.  
12719246 D.A.Smith, and M.A.Geeves (2003).
Cooperative regulation of myosin-actin interactions by a continuous flexible chain II: actin-tropomyosin-troponin and regulation by calcium.
  Biophys J, 84, 3168-3180.  
12846826 D.C.Oliveira, and F.C.Reinach (2003).
The calcium-induced switch in the troponin complex probed by fluorescent mutants of troponin I.
  Eur J Biochem, 270, 2937-2944.  
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.  
12909617 W.J.Dong, J.M.Robinson, J.Xing, and H.C.Cheung (2003).
Kinetics of conformational transitions in cardiac troponin induced by Ca2+ dissociation determined by Förster resonance energy transfer.
  J Biol Chem, 278, 42394-42402.  
11980481 J.B.Ames, N.Hamasaki, and T.Molchanova (2002).
Structure and calcium-binding studies of a recoverin mutant (E85Q) in an allosteric intermediate state.
  Biochemistry, 41, 5776-5787.
PDB code: 1la3
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
11266616 A.Ababou, and J.R.Desjarlais (2001).
Solvation energetics and conformational change in EF-hand proteins.
  Protein Sci, 10, 301-312.  
11266596 H.Aitio, T.Laakso, T.Pihlajamaa, M.Torkkeli, I.Kilpeläinen, T.Drakenberg, R.Serimaa, and A.Annila (2001).
Characterization of apo and partially saturated states of calerythrin, an EF-hand protein from S. erythraea: a molten globule when deprived of Ca(2+).
  Protein Sci, 10, 74-82.  
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.  
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
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.  
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
10373418 C.H.Ramos (1999).
Mapping subdomains in the C-terminal region of troponin I involved in its binding to troponin C and to thin filament.
  J Biol Chem, 274, 18189-18195.  
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.  
9880526 K.R.Barber, K.A.McClintock, G.A.Jamieson, R.V.Dimlich, and G.S.Shaw (1999).
Specificity and Zn2+ enhancement of the S100B binding epitope TRTK-12.
  J Biol Chem, 274, 1502-1508.  
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.  
10446160 Q.Kleerekoper, and J.A.Putkey (1999).
Drug binding to cardiac troponin C.
  J Biol Chem, 274, 23932-23939.  
10085072 T.Yuan, H.Ouyang, and H.J.Vogel (1999).
Surface exposure of the methionine side chains of calmodulin in solution. A nitroxide spin label and two-dimensional NMR study.
  J Biol Chem, 274, 8411-8420.  
10350487 Y.Luo, J.Leszyk, Y.Qian, J.Gergely, and T.Tao (1999).
Residues 48 and 82 at the N-terminal hydrophobic pocket of rabbit skeletal muscle troponin-C photo-cross-link to Met121 of troponin-I.
  Biochemistry, 38, 6678-6688.  
  9828012 A.L.Hazard, S.C.Kohout, N.L.Stricker, J.A.Putkey, and J.J.Falke (1998).
The kinetic cycle of cardiac troponin C: calcium binding and dissociation at site II trigger slow conformational rearrangements.
  Protein Sci, 7, 2451-2459.  
9560191 D.G.Vassylyev, S.Takeda, S.Wakatsuki, K.Maeda, and Y.Maéda (1998).
Crystal structure of troponin C in complex with troponin I fragment at 2.3-A resolution.
  Proc Natl Acad Sci U S A, 95, 4847-4852.
PDB code: 1a2x
9628471 D.H.MacLennan, and R.A.Reithmeier (1998).
Ion tamers.
  Nat Struct Biol, 5, 409-411.  
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.  
9519412 M.Sastry, R.R.Ketchem, O.Crescenzi, C.Weber, M.J.Lubienski, H.Hidaka, and W.J.Chazin (1998).
The three-dimensional structure of Ca(2+)-bound calcyclin: implications for Ca(2+)-signal transduction by S100 proteins.
  Structure, 6, 223-231.
PDB code: 1a03
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.  
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
9819203 X.Shao, I.Fernandez, T.C.Südhof, and J.Rizo (1998).
Solution structures of the Ca2+-free and Ca2+-bound C2A domain of synaptotagmin I: does Ca2+ induce a conformational change?
  Biochemistry, 37, 16106-16115.
PDB code: 1byn
9283081 B.Gopal, C.P.Swaminathan, S.Bhattacharya, A.Bhattacharya, M.R.Murthy, and A.Surolia (1997).
Thermodynamics of metal ion binding and denaturation of a calcium binding protein from Entamoeba histolytica.
  Biochemistry, 36, 10910-10916.  
9341121 H.M.Rarick, X.H.Tu, R.J.Solaro, and A.F.Martin (1997).
The C terminus of cardiac troponin I is essential for full inhibitory activity and Ca2+ sensitivity of rat myofibrils.
  J Biol Chem, 272, 26887-26892.  
9131994 J.Evenäs, E.Thulin, A.Malmendal, S.Forsén, and G.Carlström (1997).
NMR studies of the E140Q mutant of the carboxy-terminal domain of calmodulin reveal global conformational exchange in the Ca2+-saturated state.
  Biochemistry, 36, 3448-3457.  
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.  
9245425 S.K.Drake, M.A.Zimmer, C.L.Miller, and J.J.Falke (1997).
Optimizing the metal binding parameters of an EF-hand-like calcium chelation loop: coordinating side chains play a more important tuning role than chelation loop flexibility.
  Biochemistry, 36, 9917-9926.  
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
  9385641 S.Linse, E.Thulin, L.K.Gifford, D.Radzewsky, J.Hagan, R.R.Wilk, and K.S.Akerfeldt (1997).
Domain organization of calbindin D28k as determined from the association of six synthetic EF-hand fragments.
  Protein Sci, 6, 2385-2396.  
9188721 S.Lundberg, A.V.Buevich, I.Sethson, U.Edlund, and L.Backman (1997).
Calcium-binding mechanism of human nonerythroid alpha-spectrin EF-structures.
  Biochemistry, 36, 7199-7208.  
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.  
9053397 W.D.Kohn, C.T.Mant, and R.S.Hodges (1997).
Alpha-helical protein assembly motifs.
  J Biol Chem, 272, 2583-2586.  
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.  
8855232 D.Foguel, M.C.Suarez, C.Barbosa, J.J.Rodrigues, M.M.Sorenson, L.B.Smillie, and J.L.Silva (1996).
Mimicry of the calcium-induced conformational state of troponin C by low temperature under pressure.
  Proc Natl Acad Sci U S A, 93, 10642-10646.  
8848832 M.Ikura (1996).
Calcium binding and conformational response in EF-hand proteins.
  Trends Biochem Sci, 21, 14-17.  
8688416 S.P.Smith, K.R.Barber, S.D.Dunn, and G.S.Shaw (1996).
Structural influence of cation binding to recombinant human brain S100b: evidence for calcium-induced exposure of a hydrophobic surface.
  Biochemistry, 35, 8805-8814.  
8550567 X.Lin, D.G.Dotson, and J.A.Putkey (1996).
Covalent binding of peptides to the N-terminal hydrophobic region of cardiac troponin C has limited effects on function.
  J Biol Chem, 271, 244-249.  
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.