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Inhibition of mutant troponin C activity by an intra-domain disulphide bond

Abstract

Triggering of contraction in striated muscles involves a conformational transition in the N-terminal domain of troponin C, the calcium-binding component of thin filaments. We have designed a mutant troponin C in which the key conformational transition and the calcium-regulatory activity are reversibly blocked by the formation of a disulphide bridge. Our results may be applicable to other proteins of the same family of calcium-binding proteins.

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References

  1. Leavis, P. C. & Gergely, J. CRC Crit. Rev. Biochem. 16, 235–305 (1984).

    Article  CAS  PubMed  Google Scholar 

  2. Zot, A. S. & Potter, J. D. A. Rev. Biophys. Biophys. Chem. 16, 535–559 (1987).

    Article  CAS  Google Scholar 

  3. Satyshur, K. A. et al. J. biol. Chem. 263, 1628–1647 (1988).

    CAS  PubMed  Google Scholar 

  4. Herzberg, O. & James, M. N. G. J. molec. Biol. 203, 761–779 (1988).

    Article  CAS  PubMed  Google Scholar 

  5. Wang, C.-L. A., Grabarek, Z., Tao, T. & Gergely, J. in Calcium Binding Proteins in Health and Disease (eds Norman, A. W., Vanaman, T. C. & Means, A. R.) 440–442 (Academic, San Diego, 1987).

    Book  Google Scholar 

  6. Wang, C.-L. A., Zhan, Q., Tao, T. & Gergely, J. J. biol. Chem. 262, 9636–9640 (1987).

    CAS  PubMed  Google Scholar 

  7. Cheung, H. C. et al. Biophys. J. 55, 122a (1989).

    Google Scholar 

  8. Heidorn, D. B. & Trewhella, J. Biochemistry 27, 909–914 (1988).

    Article  CAS  PubMed  Google Scholar 

  9. Leszyk, J., Grabarek, Z., Gergely, J. & Collins, J. Biochemistry, 29, 299–304 (1990).

    Article  CAS  PubMed  Google Scholar 

  10. Robertson, S. P., Johnson, J. D. & Potter, J. D. Biophys. J. 34, 559–569 (1981).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Grabarek, Z., Drabikowski, W., Leavis, P. C., Rosenfeld, S. & Gergely, J. J. biol. Chem. 256, 13121–13127 (1981).

    CAS  PubMed  Google Scholar 

  12. Grabarek, Z., Leavis, P. C. & Gergely, J. J. biol. Chem. 261, 608–613 (1986).

    CAS  PubMed  Google Scholar 

  13. Wang, C.-L. A. & Gergely, J. Eur. J. Biochem. 154, 225–228 (1985).

    Article  Google Scholar 

  14. Sundaralingam, M., Drendel, W. & Greaser, M. Proc. natn. Acad. Sci. U.S.A. 82, 7944–7947 (1985).

    Article  CAS  ADS  Google Scholar 

  15. Reinach, F. C. & Carlsson, R. J. biol. Chem. 263, 2371–2376 (1988).

    CAS  PubMed  Google Scholar 

  16. Xu, G.-Q. & Hitchcock DeGregori, S. E. J. biol. Chem. 263, 13962–13969 (1988).

    CAS  PubMed  Google Scholar 

  17. Herzberg, O., Moult, J. & James, M. N. G. J. biol. Chem. 261, 2638–2644 (1986).

    CAS  PubMed  Google Scholar 

  18. Strynadka, N. C. J. & James, M. N. G. A. Rev. Biochem. 58, 951–998 (1989).

    Article  CAS  Google Scholar 

  19. Ingraham, R. H. & Hodges, R. S. Biochemistry 27, 5891–5898 (1988).

    Article  CAS  PubMed  Google Scholar 

  20. Fuchs, F., Liou, Y.-M. & Grabarek, Z. J. biol. Chem. 264, 20344–20349 (1989).

    CAS  PubMed  Google Scholar 

  21. Johnson, J. D., Collins, J. H. & Potter, J. D. J. biol. Chem. 253, 6451–6458 (1978).

    CAS  PubMed  Google Scholar 

  22. van Eerd, J. P. & Kawasaki, Y. Biochem. biophys. Res. Commun. 47, 859–865 (1972).

    Article  CAS  PubMed  Google Scholar 

  23. Matsumura, M. & Matthews, B. W. Science 243, 792–794 (1989).

    Article  CAS  ADS  PubMed  Google Scholar 

  24. Persechini, A. P. & Kretsinger, R. H. J. biol. Chem. 263, 12175–12178 (1988).

    CAS  PubMed  Google Scholar 

  25. Putkey, J. A., Sweeney, H. L. & Campbell, S. T. J. biol. Chem. 264, 12370–12378 (1989).

    CAS  PubMed  Google Scholar 

  26. Cachia, P. J., Sykes, B. D. & Hodges, R. S. Biochemistry 22, 4145–4152 (1983).

    Article  CAS  PubMed  Google Scholar 

  27. Dalgarno, D. et al. FEBS Lett. 150, 54–58 (1982).

    Article  CAS  Google Scholar 

  28. Leszyk, J., Collins, J. H., Leavis, P. C. & Tao, T. Biochemistry 27, 6983–6987 (1988).

    Article  CAS  PubMed  Google Scholar 

  29. Persechini, A. P. & Kretsinger, R. H. J. Cardiovasc. Pharmacol. 12, S1–S12 (1988).

    Article  CAS  PubMed  Google Scholar 

  30. Grand, R. J. A., Levine, B. A. & Perry, S. V. Biochem. J. 203, 61–68 (1982).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Kretsinger, R. H. & Nockolds, C. E. J. biol. Chem. 248, 3313–3326 (1973).

    CAS  PubMed  Google Scholar 

  32. Reid, R. E. & Hodges, R. S. J. theor. Biol. 84, 401–444 (1980).

    Article  CAS  PubMed  Google Scholar 

  33. Boguta, G., Stepkowski, D. & Bierzynski, A. J. theor. Biol. 135, 63–74 (1988).

    Article  CAS  PubMed  Google Scholar 

  34. Sekharudu, Y. C. & Sundaralingam, M. Prot. Engng. 2, 139–146 (1988).

    Article  CAS  Google Scholar 

  35. Cachia, P. J., Gariepy, J. & Hodges, R. S. in Calcium Antagonists and Cellular Physiology (eds Hidaka, H. & Hartshorne, D. J.) 63–88 (Academic, Toronto, 1985).

    Book  Google Scholar 

  36. Kretsinger, R. H. CRC. Crit. Rev. Biochem. 8, 119–174 (1980).

    Article  CAS  PubMed  Google Scholar 

  37. Gariepy, J. & Hodges, R. S. FEBS Lett. 160, 1–6 (1983).

    Article  CAS  PubMed  Google Scholar 

  38. Morris, E. P. & Lehrer, S. S. Biochemistry 23, 2214–2219 (1984).

    Article  CAS  PubMed  Google Scholar 

  39. Chong, P. C. S. & Hodges, R. S. J. biol. Chem. 257, 2549–2555 (1982).

    CAS  PubMed  Google Scholar 

  40. Bradford, M. Analyt. Biochem. 72, 248–254 (1976).

    Article  CAS  PubMed  Google Scholar 

  41. Cox, J. A., Comte, M. & Stein, E. A. Biochem. J. 195, 205–211 (1981).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Fiske, C. H. & SubbaRow, Y. J. biol. Chem. 66, 375–400 (1925).

    CAS  Google Scholar 

  43. Kunkel, T. A. Proc. natn. Acad. Sci. U.S.A. 82, 488–492 (1985).

    Article  CAS  ADS  Google Scholar 

  44. Chen, Q., Taljanidisz, J., Sarkar, S., Tao, T. & Gergely, J. FEBS Lett. 228, 22–26 (1988).

    Article  CAS  PubMed  Google Scholar 

  45. Miki, T. et al. Prot. Engng 1, 327–332 (1987).

    Article  CAS  Google Scholar 

  46. Wang, Z., Sarkar, S., Gergely, J. & Tao, T. J. biol. Chem. 256, 4953–4957 (1990).

    Google Scholar 

  47. Sanger, F., Milken, S. & Coulson, A. R. Proc. natn. Acad. Sci. U.S.A. 74, 5463–5467 (1977).

    Article  CAS  ADS  Google Scholar 

  48. Perrin, D. D. & Sayce, J. G. Talanta 14, 833–842 (1967).

    Article  CAS  PubMed  Google Scholar 

  49. Sillen, L. G. & Martel, A. E. In Stability Constants of Metal Complexes 2nd edn, Spec. Publ. No 17 (The Chemical Society, London, 1967).

    Google Scholar 

  50. Greaser, M. & Gergely, J. J. biol. Chem. 246, 4226–4233 (1971).

    CAS  PubMed  Google Scholar 

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Grabarek, Z., Tan, RY., Wang, J. et al. Inhibition of mutant troponin C activity by an intra-domain disulphide bond. Nature 345, 132–135 (1990). https://doi.org/10.1038/345132a0

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