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PDBsum entry 1avs
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protein metals Protein-protein interface(s) links
Muscle contraction PDB id
1avs

 

 

 

 

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Contents
Protein chains
81 a.a. *
Metals
_CA ×4
Waters ×93
* Residue conservation analysis
PDB id:
1avs
Name: Muscle contraction
Title: X-ray crystallographic study of calcium-saturated n-terminal domain of troponin c
Structure: Troponin c. Chain: a, b. Fragment: n-terminal domain, residues 1 - 90. Engineered: yes
Source: Gallus gallus. Chicken. Organism_taxid: 9031. Tissue: breast. Expressed in: escherichia coli. Expression_system_taxid: 562
Resolution:
1.75Å     R-factor:   0.220     R-free:   0.250
Authors: N.C.J.Strynadka,M.N.G.James
Key ref:
N.C.Strynadka et al. (1997). Structural details of a calcium-induced molecular switch: X-ray crystallographic analysis of the calcium-saturated N-terminal domain of troponin C at 1.75 A resolution. J Mol Biol, 273, 238-255. PubMed id: 9367759 DOI: 10.1006/jmbi.1997.1257
Date:
19-Sep-97     Release date:   24-Dec-97    
PROCHECK
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 Headers
 References

Protein chains
P02588  (TNNC2_CHICK) -  Troponin C, skeletal muscle from Gallus gallus
Seq:
Struc: 		163 a.a.
81 a.a.
Key:    Secondary structure  CATH domain

 

 
DOI no: 10.1006/jmbi.1997.1257 J Mol Biol 273:238-255 (1997)
PubMed id: 9367759  
 
 
Structural details of a calcium-induced molecular switch: X-ray crystallographic analysis of the calcium-saturated N-terminal domain of troponin C at 1.75 A resolution.
N.C.Strynadka, M.Cherney, A.R.Sielecki, M.X.Li, L.B.Smillie, M.N.James.
 
  ABSTRACT  
 
We have solved and refined the crystal and molecular structures of the calcium-saturated N-terminal domain of troponin C (TnC) to 1.75 A resolution. This has allowed for the first detailed analysis of the calcium binding sites of this molecular switch in the calcium-loaded state. The results provide support for the proposed binding order and qualitatively, for the affinity of calcium in the two regulatory calcium binding sites. Based on a comparison with the high-resolution apo-form of TnC we propose a possible mechanism for the calcium-mediated exposure of a large hydrophobic surface that is central to the initiation of muscle contraction within the cell.
 
  Selected figure(s)  
 
Figure 6.
Figure 6. The 12 residues of the EF-hand site I of N-TnC. In this and Figure 7, residues are color-coded according to type: aliphatic hydrophobic are green; aromatic residues are brown; methionine are yellow; positively charged resi- dues are blue; negatively charged residues are red and polar side-chains, Ser, Thr, Asn and Gln are orange and pink. Main-chain atoms C a , C, D, N are depicted in white. Calcium is shown as a magenta sphere. Water molecules (five is equatorial, nine is axial) are shown as cyan spheres. Water molecules are labelled as 5 or 9 depending on which liganding position in the EF-hand loop they occupy. Hydrogen bonds are denoted as broken yellow lines. (a) Ligand- ing residues in the 2-Ca 2+ form; (b) hydrogen bonding patterns within the 2-Ca 2+ form; (c) a similar view of site I in the apo 0-Ca 2+ form of N-TnC. The Figure was generated using Raster 3D (Merrit & Murphy, 1994). 		Figure 7.
Figure 7. The 12 residues of the EF-hand site II of N-TnC. Calcium is shown as a magenta sphere. Water molecules (water 9 is in the axial position) are shown as cyan spheres. Hydrogen bonds are denoted as broken yellow lines. (a) Liganding residues in the 2-Ca 2+ form; (b) hydrogen bonding patterns within the 2-Ca 2+ form; (c) a similar view of site II in the apo 0-Ca 2+ form of N-TnC.
 
  The above figures are reprinted by permission from Elsevier: J Mol Biol (1997, 273, 238-255) copyright 1997.  
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
19439414 J.R.Pinto, M.S.Parvatiyar, M.A.Jones, J.Liang, M.J.Ackerman, and J.D.Potter (2009).
A functional and structural study of troponin C mutations related to hypertrophic cardiomyopathy.
  J Biol Chem, 284, 19090-19100.  
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.  
18329314 P.Trojan, N.Krauss, H.W.Choe, A.Giessl, A.Pulvermüller, and U.Wolfrum (2008).
Centrins in retinal photoreceptor cells: regulators in the connecting cilium.
  Prog Retin Eye Res, 27, 237-259.  
18231806 Y.M.Liou, S.C.Kuo, and S.R.Hsieh (2008).
Differential effects of a green tea-derived polyphenol (-)-epigallocatechin-3-gallate on the acidosis-induced decrease in the Ca(2+) sensitivity of cardiac and skeletal muscle.
  Pflugers Arch, 456, 787-800.  
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.  
16128816 H.Tanaka, Y.Takeya, T.Doi, F.Yumoto, M.Tanokura, I.Ohtsuki, K.Nishita, and T.Ojima (2005).
Comparative studies on the functional roles of N- and C-terminal regions of molluskan and vertebrate troponin-I.
  FEBS J, 272, 4475-4486.  
15689515 L.Deng, E.S.Vysotski, S.V.Markova, Z.J.Liu, J.Lee, J.Rose, and B.C.Wang (2005).
All three Ca2+-binding loops of photoproteins bind calcium ions: the crystal structures of calcium-loaded apo-aequorin and apo-obelin.
  Protein Sci, 14, 663-675.
PDB codes: 1sl7 1sl8
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
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.  
12846843 Y.M.Liou, and M.W.Chen (2003).
Calcium-dependent protein-protein interactions induce changes in proximity relationships of Cys48 and Cys64 in chicken skeletal troponin I.
  Eur J Biochem, 270, 3092-3100.  
12397067 J.P.Davis, J.A.Rall, P.J.Reiser, L.B.Smillie, and S.B.Tikunova (2002).
Engineering competitive magnesium binding into the first EF-hand of skeletal troponin C.
  J Biol Chem, 277, 49716-49726.  
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.  
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
11119639 B.V.Reddy, W.W.Li, I.N.Shindyalov, and P.E.Bourne (2001).
Conserved key amino acid positions (CKAAPs) derived from the analysis of common substructures in proteins.
  Proteins, 42, 148-163.  
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.  
11389591 S.Kim, D.N.Cullis, L.A.Feig, and J.D.Baleja (2001).
Solution structure of the Reps1 EH domain and characterization of its binding to NPF target sequences.
  Biochemistry, 40, 6776-6785.
PDB code: 1fi6
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.  
11114499 A.Lewit-Bentley, and S.Réty (2000).
EF-hand calcium-binding proteins.
  Curr Opin Struct Biol, 10, 637-643.  
  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
10757979 J.L.Enmon, T.de Beer, and M.Overduin (2000).
Solution structure of Eps15's third EH domain reveals coincident Phe-Trp and Asn-Pro-Phe binding sites.
  Biochemistry, 39, 4309-4319.
PDB code: 1c07
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.  
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
10209279 A.Yu, L.Ballard, L.Smillie, J.Pearlstone, D.Foguel, J.Silva, A.Jonas, and J.Jonas (1999).
Effects of high pressure and temperature on the wild-type and F29W mutant forms of the N-domain of avian troponin C.
  Biochim Biophys Acta, 1431, 53-63.  
10402470 H.Terami, B.D.Williams, S.Kitamura, Y.Sakube, S.Matsumoto, S.Doi, T.Obinata, and H.Kagawa (1999).
Genomic organization, expression, and analysis of the troponin C gene pat-10 of Caenorhabditis elegans.
  J Cell Biol, 146, 193-202.  
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.  
10233080 M.Regnier, A.J.Rivera, P.B.Chase, L.B.Smillie, and M.M.Sorenson (1999).
Regulation of skeletal muscle tension redevelopment by troponin C constructs with different Ca2+ affinities.
  Biophys J, 76, 2664-2672.  
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.  
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 1zam 1zas
10411658 W.Klaus, S.Grzesiek, A.M.Labhardt, P.Buchwald, W.Hunziker, M.D.Gross, and D.A.Kallick (1999).
NMR investigation and secondary structure of domains I and II of rat brain calbindin D28k (1-93).
  Eur J Biochem, 262, 933-938.  
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.  
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
9753463 J.Evenäs, A.Malmendal, E.Thulin, G.Carlström, and S.Forsén (1998).
Ca2+ binding and conformational changes in a calmodulin domain.
  Biochemistry, 37, 13744-13754.  
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.  
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
9721102 T.de Beer, R.E.Carter, K.E.Lobel-Rice, A.Sorkin, and M.Overduin (1998).
Structure and Asn-Pro-Phe binding pocket of the Eps15 homology domain.
  Science, 281, 1357-1360.
PDB code: 1eh2
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 codes are shown on the right.

 

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