Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

Structures of the troponin C regulatory domains in the apo and calcium-saturated states

Nature Structural Biology volume 2, pages 784–789 (1995)Cite this article

Abstract

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.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Similar content being viewed by others

References

  1. Leavis, P.C. & Gergeley, J. Thin filament proteins and thin filament-linked regulation of vertebrate muscle contraction. CRC Crit. Rev. Biochem. 16, 235–305 (1984).

    Article  CAS  Google Scholar 

  2. Zot, A.S. & Potter, J.D. Structural aspects of troponin-tropomyosin regulation of skeletal muscle contraction. A. Rev. Biophys. biophys. Chem. 16, 535–559 (1987).

    Article  CAS  Google Scholar 

  3. Ohtsuki, I., Maruyama, K. & Ebashi, S. Regulatory and cytoskeletal proteins of vertebrate skeletal muscle. Adv. Protein Chem. 38, 1–67 (1986).

    Article  CAS  Google Scholar 

  4. Farah, C.S. & Reinach, F.C. The troponin complex and regulation of muscle contraction. FASEB J. in the press (1995).

    Google Scholar 

  5. Herzberg, O. & James, M.N.G. Refined crystal structure of troponin C from turkey skeletal muscle at 2.0 Å resolution. J. molec. Biol. 203, 761–779 (1988).

    Article  CAS  Google Scholar 

  6. Satyshur, K.A. et al. Refined structure of chicken skeletal muscle troponin C in the two- calcium state at 2-Å resolution. J. biol. Chem. 263, 1628–1647 (1988).

    CAS  PubMed  Google Scholar 

  7. Grabarek, Z., Tao, T. & Gergely, J. Molecular mechanism of troponin C function. J. Muscle Res. Cell Motil. 13, 383–393 (1992).

    Article  CAS  Google Scholar 

  8. Farah, C.S. et al. Structural and regulatory functions of the NH2-and COOH-terminal regions of skeletal muscle troponin-I. J. biol. Chem. 269, 5230–5240 (1994).

    CAS  PubMed  Google Scholar 

  9. Herzberg, O. & James, M.N.G. Structure of the calcium regulatory muscle protein troponin C at 2.8 Å resolution. Nature 313, 653–659 (1985).

    Article  CAS  Google Scholar 

  10. Herzberg, O., Moult, J. & James, M.N.G. A model for the Ca2+-induced conformational transition of troponin C. J. biol. Chem. 261, 2638–2644 (1986).

    CAS  PubMed  Google Scholar 

  11. Gagné, S.M. et al. Quantification of the calcium-induced secondary structural changes in the regulatory domain of troponin C. Prot. Sci. 3, 1961–1974 (1994).

    Article  Google Scholar 

  12. Li, M.X. et al. Properties of isolated recombinant N and C domains of chicken troponin C. Biochemistry 33, 917–925 (1994).

    Article  CAS  Google Scholar 

  13. Slupsky, C.M., Reinach, F.C., Kay, C.M. & Sykes, B.D. Calcium-induced dimerization of troponin C: mode of interaction and use of trifluoroethanol as a denaturant of quaternary structure. Biochemistry, 34, 7365–7375 (1995).

    Article  CAS  Google Scholar 

  14. Burgering, M.J.M., Boelens, R., Caffrey, M., Breg, J.N. & Kaptein, R. Observation of inter-subunit nuclear Overhauser effects in a dimeric protein. FEBS Lett. 330, 105–109 (1993).

    Article  CAS  Google Scholar 

  15. Laskowski, R.A., MacArthur, M.W., Moss, D.S. & Thornton, J.M. PROCHECK: A program to check the stereochemical quality of protein structures. J. appl. Crystallogr. 26, 283–290 (1993).

    Article  CAS  Google Scholar 

  16. Findlay, W.A., Sönnichsen, F.D. & Sykes, B.D. Solution structure of the TR1C fragment of skeletal muscle. J. biol. Chem. 269, 6773–6778.

  17. Skelton, J.N., Kördel, J., Akke, M., Forsén, S. & Chazin, W.J. Signal transduction versus buffering activity in Ca2+-binding proteins. Nature struct. Biol. 1, 239–245 (1994).

    Article  CAS  Google Scholar 

  18. Zhang, M., Tanaka, T. & Ikura, M. Calcium-induced conformational transition revealed by the solutison structure of apo calmodulin. Nature struct. Biol. 2, 758–767 (1995).

    Article  CAS  Google Scholar 

  19. Babu, Y.S., Bugg, C.E. & Cook, W.J. Structure of calmodulin refined at 2.2 Å resolution. J. molec. Biol. 203, 191–204 (1988).

    Article  Google Scholar 

  20. Swain, A.L., Kretsinger, R.H. & Amma, E.L. Restrained least squares refinement of native (calcium) and cadmium-substituted carp parvalbumin using X-ray crystallographic data at 1.6 Å resolution. J. biol. Chem. 264, 16620–16628 (1989).

    CAS  PubMed  Google Scholar 

  21. Ahmed, F.R. et al. Structure of oncomodulin refined at 1.85 Å resolution. An example of extensive molecular aggregation via Ca2+. J. molec. Biol. 216, 127–140 (1990).

    Article  CAS  Google Scholar 

  22. Ikura, M. et al. Solution structure of a calmodulin-target peptide complex by multidimensional NMR. Science 256, 632–638 (1992).

    Article  CAS  Google Scholar 

  23. Rayment, I. et al. Three-dimensional structure of myosin subfragment-1: a molecular motor. Science 261, 50–58 (1993).

    Article  CAS  Google Scholar 

  24. Xie, X. et al. Structure of the regulatory domain of scallop myosin at 2.8 Å resolution. Nature 368, 306–312 (1994).

    Article  CAS  Google Scholar 

  25. Jeener, J., Meier, B.H., Bachmann, P. & Ernst, R.R. Investigation of exchange processes by two dimensional NMR spectroscopy. J. chem. Phys. 71, 4546–4553 (1979).

    Article  CAS  Google Scholar 

  26. Macura, S. & Ernst, R.R. Elucidation of cross relaxation in liquids by two-dimensional NMR spectroscopy. Molec. Phys. 41, 95–117 (1980).

    Article  CAS  Google Scholar 

  27. Kay, L.E., Marion, D. & Bax, A. Practical aspects of 3D heteronuclear NMR of proteins. J. magn. Res. 84, 72–84 (1989).

    CAS  Google Scholar 

  28. Ikura, M., Kay, L.E., Tschudin, R. & Bax, A. Three-dimensional NOESY-HMQC spectroscopy of a 13C-labeled protein. J. magn. Reson. 86, 204–209 (1990).

    CAS  Google Scholar 

  29. Strynadka, N.C.J. & James, M.N.G. Crystal structures of the helix-loop-helix calcium- binding proteins. A. Rev. Biochem. 58, 951–998 (1989).

    Article  CAS  Google Scholar 

  30. Kay, L.E. & Bax, A. New methods for the measurement of NH-CaH coupling constants in 15N-labeled proteins. J magn. Res. 86, 110–126 (1990).

    CAS  Google Scholar 

  31. Sykes, B.D., Slupsky, C.M., Wishart, D.S., Sönnichsen, F.D. & Gagné, S.M. NMR as a Structural Tool for Macromolecules: Current Status and Future Directions (Plenum Press, New York, in the press).

  32. Havel, T.F. An evaluation of computational strategies for use in the determination of protein structure from distance constraints obtained by nuclear magnetic resonance. Prog. Biophys. molec. Biol. 56, 45–78 (1991).

    Article  Google Scholar 

Download references

Author information

Author notes

  1. Sakae Tsuda

    Present address: Bioscience and Chemistry Division, Hokkaido National Industrial Research Institute, Toyohira, Sapporo, 06Z, Japan

Authors and Affiliations

  1. Department of Biochemistry, Medical Research Council Group in Protein Structure and Function, University of Alberta, Edmonton, T6G 2H7, Canada

    Stéphane M. Gagné, Monica X. Li, Lawrence B. Smillie & Brian D. Sykes

Authors
  1. Stéphane M. Gagné
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Sakae Tsuda
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Monica X. Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Lawrence B. Smillie
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Brian D. Sykes
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Gagné, S., Tsuda, S., Li, M. et al. Structures of the troponin C regulatory domains in the apo and calcium-saturated states. Nat Struct Mol Biol 2, 784–789 (1995). https://doi.org/10.1038/nsb0995-784

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nsb0995-784

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing