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Heterodimeric structure of superoxide dismutase in complex with its metallochaperone

Nature Structural Biology volume 8, pages 751–755 (2001)Cite this article

Abstract

The copper chaperone for superoxide dismutase (CCS) activates the eukaryotic antioxidant enzyme copper, zinc superoxide dismutase (SOD1). The 2.9 Å resolution structure of yeast SOD1 complexed with yeast CCS (yCCS) reveals that SOD1 interacts with its metallochaperone to form a complex comprising one monomer of each protein. The heterodimer interface is remarkably similar to the SOD1 and yCCS homodimer interfaces. Striking conformational rearrangements are observed in both the chaperone and target enzyme upon complex formation, and the functionally essential C-terminal domain of yCCS is well positioned to play a key role in the metal ion transfer mechanism. This domain is linked to SOD1 by an intermolecular disulfide bond that may facilitate or regulate copper delivery.

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Figure 1: Structure of the complex between SOD1 and yCCS.
Figure 2: Comparison of the heterodimeric complex with the SOD1 and yCCS homodimers.
Figure 3: Formation of an intermolecular disulfide bond between the SOD1 S–S subloop and yCCS domain III.
Figure 4: Proposed mechanism of copper transfer.

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References

  1. Holm, R.H., Kennepohl, P. & Solomon, E.I. Chem. Rev. 96, 2239–2314 (1996).

    Article  CAS  Google Scholar 

  2. Radisky, D. & Kaplan, J. J. Biol. Chem. 274, 4481–4484 (1999).

    Article  CAS  Google Scholar 

  3. Rosenzweig, A.C. Acc. Chem. Res. 34, 119–128 (2001).

    Article  CAS  Google Scholar 

  4. Rae, T.D., Schmidt, P.J., Pufahl, R.A., Culotta, V.C. & O'Halloran, T.V. Science 284, 805–808 (1999).

    Article  CAS  Google Scholar 

  5. McCord, J.M. & Fridovich, I. J. Biol. Chem. 244, 6049–6055 (1969).

    CAS  PubMed  Google Scholar 

  6. Gaudette, M., Hirano, M. & Siddique, T. Amyotroph. Lateral Sc. 1, 83–89 (2000).

    CAS  Google Scholar 

  7. Culotta, V.C. et al. J. Biol. Chem. 272, 23469–23472 (1997).

    Article  CAS  Google Scholar 

  8. Pufahl, R.A. et al. Science 278, 853–856 (1997).

    Article  CAS  Google Scholar 

  9. Srinivasan, C., Posewitz, M.C., George, G.N. & Winge, D.R. Biochemistry 37, 7572–7577 (1998).

    Article  CAS  Google Scholar 

  10. Bertini, I., Mangani, S. & Viezzoli, M.S. Adv. Inorg. Chem. 45, 127–250 (1997).

    Article  Google Scholar 

  11. Lamb, A.L., Wernimont, A.K., Pufahl, R.A., O'Halloran, T.V. & Rosenzweig, A.C. Nature Struct. Biol. 6, 724–729 (1999).

    Article  CAS  Google Scholar 

  12. Lamb, A.L., Wernimont, A.K., Pufahl, R.A., O'Halloran, T.V. & Rosenzweig, A.C. Biochemistry 39, 1589–1595 (2000).

    Article  CAS  Google Scholar 

  13. Rosenzweig, A.C. et al. Structure 7, 605–617 (1999).

    Article  CAS  Google Scholar 

  14. Schmidt, P.J. et al. J. Biol. Chem. 274, 23719–23725 (1999).

    Article  CAS  Google Scholar 

  15. Zhu, H. et al. Biochemistry 39, 5413–5421 (2000).

    Article  CAS  Google Scholar 

  16. Eisses, J.F., Stasser, J.P., Ralle, M., Kaplan, J.H. & Blackburn, N.J. Biochemistry 39, 7337–7342 (2000).

    Article  CAS  Google Scholar 

  17. Lamb, A.L., Torres, A.S., O'Halloran, T.V. & Rosenzweig, A.C. Biochemistry 39, 14720–14727 (2000).

    Article  CAS  Google Scholar 

  18. Valentine, J.S. & Pantoliano, M.W. In Copper proteins (ed. Spiro, T.G.) 291–358 (Wiley-Interscience, New York; 1981).

    Google Scholar 

  19. Djinovic, K. et al. J. Mol. Biol. 225, 791–809 (1992).

    Article  CAS  Google Scholar 

  20. Schmidt, P.J., Kunst, C. & Culotta, V.C. J. Biol. Chem. 275, 33771–33776 (2000).

    Article  CAS  Google Scholar 

  21. Poulos, T.L. Nature Struct. Biol. 6, 709–711 (1999).

    Article  CAS  Google Scholar 

  22. Falconi, M., Iovino, M. & Desideri, A. Structure 7, 903–908 (1999).

    Article  CAS  Google Scholar 

  23. Hall, L.T. et al. Biochemistry 39, 3611–3623 (2000).

    Article  CAS  Google Scholar 

  24. Bordo, D., Djinovic, K. & Bolognesi, M. J. Mol. Biol. 238, 366–386 (1994).

    Article  CAS  Google Scholar 

  25. Getzoff, E.D. et al. Nature 306, 287–290 (1983).

    Article  CAS  Google Scholar 

  26. Fisher, C.L., Cabelli, D.E., Tainer, J.A., Hallewell, R.A. & Getzoff, E.D. Proteins 19, 24–34 (1994).

    Article  CAS  Google Scholar 

  27. Altschul, S.F. et al. Nucleic Acids Res. 25, 3389–3402 (1997).

    Article  CAS  PubMed Central  Google Scholar 

  28. Rae, T.D., Torres, A.S., Pufahl, R.A. & O'Halloran, T.V. J. Biol. Chem. 276, 5166–5176 (2001).

    Article  CAS  Google Scholar 

  29. Dancis, A., Haile, D., Yuan, D.S. & Klausner, R.D. J. Biol. Chem. 269, 25660–25667 (1994).

    CAS  PubMed  Google Scholar 

  30. Knight, S.A.B., Labbe, S., Kwon, L.F., Kosman, D.J. & Thiele, D.J. Genes Dev. 10, 1917–1929 (1996).

    Article  CAS  Google Scholar 

  31. Maret, W. & Vallee, B.L. Proc. Natl. Acad. Sci. USA 95, 3478–3482 (1998).

    Article  CAS  Google Scholar 

  32. Rothstein, J.D. et al. J. Neurochemistry 72, 422–429 (1999).

    Article  CAS  Google Scholar 

  33. Bruijn, L.I. et al. Science 281, 1851–1854 (1998).

    Article  CAS  Google Scholar 

  34. Johnston, J.A., Dalton, M.J., Gurney, M.E. & Kopito, R.R. Proc. Natl. Acad. Sci. USA 97, 12571–12576 (2000).

    Article  CAS  Google Scholar 

  35. Hausinger, R.P., Colpas, G.J. & Soriano, A. ASM News 67, 78–84 (2001).

    Google Scholar 

  36. Nguyen, H.-H.T., Ge, J., Perlstein, D.L. & Stubbe, J. Proc. Natl. Acad. Sci. USA 96, 12339–12344 (1999).

    Article  CAS  Google Scholar 

  37. Agar, J.N. et al. Biochemistry 39, 7856–7862 (2000).

    Article  CAS  Google Scholar 

  38. Allen, R.M. et al. J. Biol. Chem. 274, 15869–15874 (1999).

    Article  CAS  Google Scholar 

  39. Otwinowski, Z. & Minor, W. Methods Enzymol. 276, 307–326 (1997).

    Article  CAS  Google Scholar 

  40. Collaborative Computational Project, Number 4. Acta Crystallogr. D 50, 760–763 (1994).

  41. Jones, T.A., Zou, J.-Y., Cowan, S.W. & Kjeldgaard, M. Acta Crystallogr. A 47, 110–119 (1991).

    Article  Google Scholar 

  42. McRee, D.E. J. Struct. Biol. 125, 156–165 (1999).

    Article  CAS  Google Scholar 

  43. Brünger, A.T. et al. Acta Crystallogr. D 54, 905–921 (1998).

    Article  PubMed Central  Google Scholar 

  44. Laskowski, R.A. J. Appl. Crystallogr. 26, 283–291 (1993).

    Article  CAS  Google Scholar 

  45. Kraulis, P.J. J. Appl. Crystallogr. 24, 946–950 (1991).

    Article  Google Scholar 

  46. Merritt, E.A. & Bacon, D.J. Methods Enzymol. 277, 505–524 (1997).

    Article  CAS  PubMed Central  Google Scholar 

  47. Esnouf, R.M. J. Mol. Graph. Model. 15, 132–143 (1997).

    Article  CAS  Google Scholar 

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Acknowledgements

This work was supported by an NIH grant to A.C.R., by a grant from the ALS Association to A.C.R. and by an NIH NRSA Fellowship to A.L.L. The DND-CAT Synchrotron Research Center at the Advanced Photon Source is supported by the E.I. DuPont de Nemours & Co., the Dow Chemical Co., the State of Illinois, the U. S. Department of Energy and the NSF.

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Authors and Affiliations

  1. Department of Biochemistry, Molecular Biology and Cell Biology, Northwestern University, Evanston, 60208, Illinois, USA

    Audrey L. Lamb, Thomas V. O'Halloran & Amy C. Rosenzweig

  2. Department of Chemistry, Northwestern University, Evanston, 60208, Illinois, USA

    Andrew S. Torres, Thomas V. O'Halloran & Amy C. Rosenzweig

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  1. Audrey L. Lamb
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  2. Andrew S. Torres
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  4. Amy C. Rosenzweig
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Correspondence to Amy C. Rosenzweig.

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Lamb, A., Torres, A., O'Halloran, T. et al. Heterodimeric structure of superoxide dismutase in complex with its metallochaperone. Nat Struct Mol Biol 8, 751–755 (2001). https://doi.org/10.1038/nsb0901-751

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