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PDBsum entry 1yv0

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protein metals Protein-protein interface(s) links
Contractile protein PDB id
1yv0
Jmol
Contents
Protein chains
85 a.a. *
116 a.a. *
148 a.a. *
Metals
_MG ×2
* Residue conservation analysis
PDB id:
1yv0
Name: Contractile protein
Title: Crystal structure of skeletal muscle troponin in the ca2+- free state
Structure: Troponin t, fast skeletal muscle isoforms. Chain: t. Synonym: troponin t2. Engineered: yes. Troponin i, fast skeletal muscle. Chain: i. Synonym: troponin i, fast-twitch isoform. Engineered: yes. Troponin c, skeletal muscle.
Source: Gallus gallus. Chicken. Organism_taxid: 9031. Expressed in: escherichia coli. Expression_system_taxid: 562. Gene: tnnc2. Expression_system_taxid: 562
Biol. unit: Hexamer (from PQS)
Resolution:
7.00Å     R-factor:   0.358     R-free:   0.359
Authors: M.V.Vinogradova,D.B.Stone,G.G.Malanina,C.Karatzaferi, R.Cooke,R.A.Mendelson,R.J.Fletterick
Key ref:
M.V.Vinogradova et al. (2005). Ca(2+)-regulated structural changes in troponin. Proc Natl Acad Sci U S A, 102, 5038-5043. PubMed id: 15784741 DOI: 10.1073/pnas.0408882102
Date:
14-Feb-05     Release date:   12-Apr-05    
PROCHECK
Go to PROCHECK summary
 Headers
 References

Protein chain
Pfam   ArchSchema ?
P12620  (TNNT3_CHICK) -  Troponin T, fast skeletal muscle isoforms
Seq:
Struc:
263 a.a.
85 a.a.
Protein chain
Pfam   ArchSchema ?
P68246  (TNNI2_CHICK) -  Troponin I, fast skeletal muscle
Seq:
Struc:
183 a.a.
116 a.a.*
Protein chain
Pfam   ArchSchema ?
P02588  (TNNC2_CHICK) -  Troponin C, skeletal muscle
Seq:
Struc:
163 a.a.
148 a.a.
Key:    PfamA domain  PfamB domain  Secondary structure
* PDB and UniProt seqs differ at 2 residue positions (black crosses)

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

 

 
DOI no: 10.1073/pnas.0408882102 Proc Natl Acad Sci U S A 102:5038-5043 (2005)
PubMed id: 15784741  
 
 
Ca(2+)-regulated structural changes in troponin.
M.V.Vinogradova, D.B.Stone, G.G.Malanina, C.Karatzaferi, R.Cooke, R.A.Mendelson, R.J.Fletterick.
 
  ABSTRACT  
 
Troponin senses Ca2+ to regulate contraction in striated muscle. Structures of skeletal muscle troponin composed of TnC (the sensor), TnI (the regulator), and TnT (the link to the muscle thin filament) have been determined. The structure of troponin in the Ca(2+)-activated state features a nearly twofold symmetrical assembly of TnI and TnT subunits penetrated asymmetrically by the dumbbell-shaped TnC subunit. Ca ions are thought to regulate contraction by controlling the presentation to and withdrawal of the TnI inhibitory segment from the thin filament. Here, we show that the rigid central helix of the sensor binds the inhibitory segment of TnI in the Ca(2+)-activated state. Comparison of crystal structures of troponin in the Ca(2+)-activated state at 3.0 angstroms resolution and in the Ca(2+)-free state at 7.0 angstroms resolution shows that the long framework helices of TnI and TnT, presumed to be a Ca(2+)-independent structural domain of troponin are unchanged. Loss of Ca ions causes the rigid central helix of the sensor to collapse and to release the inhibitory segment of TnI. The inhibitory segment of TnI changes conformation from an extended loop in the presence of Ca2+ to a short alpha-helix in its absence. We also show that Anapoe, a detergent molecule, increases the contractile force of muscle fibers and binds specifically, together with the TnI switch helix, in a hydrophobic pocket of TnC upon activation by Ca ions.
 
  Selected figure(s)  
 
Figure 3.
Fig. 3. Superposition of the structures of chicken skeletal muscle troponin and human cardiac troponin in the Ca^2+-saturated state. The structure of cardiac troponin (28) (PDB ID code 1J1D [PDB] ; chains A, B, and C) is shown in gray. Arrows indicate deviations.
Figure 5.
Fig. 5. Cartoon representation of the conformational changes occurring in troponin during muscle contraction. For color coding, see the legend to Fig. 1. Ca ions are shown as black circles. The hydrophobic pocket opened in the N-terminal lobe of TnC is colored in green. The switch segment and the inhibitory segment of TnI are indicated.
 
  Figures were selected by an automated process.  

Literature references that cite this PDB file's key reference

  PubMed id Reference
21310275 D.M.Jordan, A.Kiezun, S.M.Baxter, V.Agarwala, R.C.Green, M.F.Murray, T.Pugh, M.S.Lebo, H.L.Rehm, B.H.Funke, and S.R.Sunyaev (2011).
Development and validation of a computational method for assessment of missense variants in hypertrophic cardiomyopathy.
  Am J Hum Genet, 88, 183-192.  
21148419 R.J.Perz-Edwards, T.C.Irving, B.A.Baumann, D.Gore, D.C.Hutchinson, U.Kržič, R.L.Porter, A.B.Ward, and M.K.Reedy (2011).
X-ray diffraction evidence for myosin-troponin connections and tropomyosin movement during stretch activation of insect flight muscle.
  Proc Natl Acad Sci U S A, 108, 120-125.  
  21250664 S.R.Martin, G.Avella, M.Adrover, G.F.de Nicola, B.Bullard, and A.Pastore (2011).
Binding properties of the calcium-activated F2 isoform of Lethocerus troponin C.
  Biochemistry, 50, 1839-1847.  
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.  
19900412 A.Cammarato, R.Craig, and W.Lehman (2010).
Electron microscopy and three-dimensional reconstruction of native thin filaments reveal species-specific differences in regulatory strand densities.
  Biochem Biophys Res Commun, 391, 193-197.  
19920153 D.Kowlessur, and L.S.Tobacman (2010).
Troponin regulatory function and dynamics revealed by H/D exchange-mass spectrometry.
  J Biol Chem, 285, 2686-2694.  
20025974 D.M.Paul, J.M.Squire, and E.P.Morris (2010).
A novel approach to the structural analysis of partially decorated actin based filaments.
  J Struct Biol, 170, 278-285.  
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
20139080 T.Aihara, M.Nakamura, S.Ueki, H.Hara, M.Miki, and T.Arata (2010).
Switch action of troponin on muscle thin filament as revealed by spin labeling and pulsed EPR.
  J Biol Chem, 285, 10671-10677.  
19108638 D.A.Patel, and D.D.Root (2009).
Close proximity of myosin loop 3 to troponin determined by triangulation of resonance energy transfer distance measurements.
  Biochemistry, 48, 357-369.  
19321455 D.M.Paul, E.P.Morris, R.W.Kensler, and J.M.Squire (2009).
Structure and orientation of troponin in the thin filament.
  J Biol Chem, 284, 15007-15015.  
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.  
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.  
19416847 M.V.Vinogradova, G.G.Malanina, A.S.Reddy, and R.J.Fletterick (2009).
Structure of the complex of a mitotic kinesin with its calcium binding regulator.
  Proc Natl Acad Sci U S A, 106, 8175-8179.
PDB code: 3h4s
19384409 R.Jain, S.Kumar, S.Gourinath, S.Bhattacharya, and A.Bhattacharya (2009).
N- and C-terminal domains of the calcium binding protein EhCaBP1 of the parasite entamoeba histolytica display distinct functions.
  PLoS ONE, 4, e5269.  
19483081 T.Kobayashi, S.E.Patrick, and M.Kobayashi (2009).
Ala scanning of the inhibitory region of cardiac troponin I.
  J Biol Chem, 284, 20052-20060.  
19379756 W.A.Mudalige, T.C.Tao, and S.S.Lehrer (2009).
Ca2+-dependent photocrosslinking of tropomyosin residue 146 to residues 157-163 in the C-terminal domain of troponin I in reconstituted skeletal muscle thin filaments.
  J Mol Biol, 389, 575-583.  
19341744 W.Lehman, A.Galińska-Rakoczy, V.Hatch, L.S.Tobacman, and R.Craig (2009).
Structural basis for the activation of muscle contraction by troponin and tropomyosin.
  J Mol Biol, 388, 673-681.  
18514658 A.Galińska-Rakoczy, P.Engel, C.Xu, H.Jung, R.Craig, L.S.Tobacman, and W.Lehman (2008).
Structural basis for the regulation of muscle contraction by troponin and tropomyosin.
  J Mol Biol, 379, 929-935.  
18775725 H.S.Jung, and R.Craig (2008).
Ca2+ -induced tropomyosin movement in scallop striated muscle thin filaments.
  J Mol Biol, 383, 512-519.  
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.  
18386050 J.R.Pinto, T.Veltri, and M.M.Sorenson (2008).
Modulation of troponin C affinity for the thin filament by different cross-bridge states in skinned skeletal muscle fibers.
  Pflugers Arch, 456, 1177-1187.  
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.  
18281058 M.D.Jeyasingham, A.Artigues, O.W.Nadeau, and G.M.Carlson (2008).
Structural evidence for co-evolution of the regulation of contraction and energy production in skeletal muscle.
  J Mol Biol, 377, 623-629.  
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.  
17912755 P.M.Mohan, S.Mukherjee, and K.V.Chary (2008).
Differential native state ruggedness of the two Ca2+-binding domains in a Ca2+ sensor protein.
  Proteins, 70, 1147-1153.  
18162178 R.J.Solaro, P.Rosevear, and T.Kobayashi (2008).
The unique functions of cardiac troponin I in the control of cardiac muscle contraction and relaxation.
  Biochem Biophys Res Commun, 369, 82-87.  
18433059 R.M.Hoffman, and B.D.Sykes (2008).
Isoform-specific variation in the intrinsic disorder of troponin I.
  Proteins, 73, 338-350.  
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.  
17260966 B.J.Biesiadecki, S.M.Chong, T.M.Nosek, and J.P.Jin (2007).
Troponin T core structure and the regulatory NH2-terminal variable region.
  Biochemistry, 46, 1368-1379.  
  17554181 F.Yumoto, K.Nagata, Y.Miyauchi, T.Ojima, H.Tanaka, K.Nishita, I.Ohtsuki, and M.Tanokura (2007).
Crystallization and preliminary X-ray analysis of the Ca2+-bound C-terminal lobe of troponin C in complex with a troponin I-derived peptide fragment from Akazara scallop.
  Acta Crystallogr Sect F Struct Biol Cryst Commun, 63, 535-537.  
17602701 M.V.Westfall, and J.M.Metzger (2007).
Single amino acid substitutions define isoform-specific effects of troponin I on myofilament Ca2+ and pH sensitivity.
  J Mol Cell Cardiol, 43, 107-118.  
17436057 S.E.Boussouf, R.Maytum, K.Jaquet, and M.A.Geeves (2007).
Role of tropomyosin isoforms in the calcium sensitivity of striated muscle thin filaments.
  J Muscle Res Cell Motil, 28, 49-58.  
17396243 S.M.Day, M.V.Westfall, and J.M.Metzger (2007).
Tuning cardiac performance in ischemic heart disease and failure by modulating myofilament function.
  J Mol Med, 85, 911-921.  
17008370 B.Schoffstall, N.M.Brunet, S.Williams, V.F.Miller, A.T.Barnes, F.Wang, L.A.Compton, L.A.McFadden, D.W.Taylor, M.Seavy, R.Dhanarajan, and P.B.Chase (2006).
Ca2+ sensitivity of regulated cardiac thin filament sliding does not depend on myosin isoform.
  J Physiol, 577, 935-944.  
16857209 D.R.Swartz, Z.Yang, A.Sen, S.B.Tikunova, and J.P.Davis (2006).
Myofibrillar troponin exists in three states and there is signal transduction along skeletal myofibrillar thin filaments.
  J Mol Biol, 361, 420-435.  
16258047 M.G.Bell, E.B.Lankford, G.E.Gonye, G.C.Ellis-Davies, D.A.Martyn, M.Regnier, and R.J.Barsotti (2006).
Kinetics of cardiac thin-filament activation probed by fluorescence polarization of rhodamine-labeled troponin C in skinned guinea pig trabeculae.
  Biophys J, 90, 531-543.  
16415057 T.M.Blumenschein, D.B.Stone, R.J.Fletterick, R.A.Mendelson, and B.D.Sykes (2006).
Dynamics of the C-terminal region of TnI in the troponin complex in solution.
  Biophys J, 90, 2436-2444.  
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.  
16981728 Z.Zhang, B.J.Biesiadecki, and J.P.Jin (2006).
Selective deletion of the NH2-terminal variable region of cardiac troponin T in ischemia reperfusion by myofibril-associated mu-calpain cleavage.
  Biochemistry, 45, 11681-11694.  
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.  
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.