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Structure of 20S proteasome from yeast at 2.4Å resolution

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Abstract

The crystal structure of the 20S proteasome from the yeast Saccharomyces cerevisiae shows that its 28 protein subunits are arranged as an (α1...α7, β1...β7)2 complex in four stacked rings and occupy unique locations. The interior of the particle, which harbours the active sites, is only accessible by some very narrow side entrances. The β-type subunits are synthesized as proproteins before being proteolytically processed for assembly into the particle. The proforms of three of the seven different β-type subunits, (β1/PRE3, β2/PUP1 and β5/PRE2, are cleaved between the threonine at position 1 and the last glycine of the pro-sequence, with release of the active-site residue Thr 1. These three β-type subunits have inhibitor-binding sites, indicating that PRE2 has a chymotrypsin-like and a trypsin-like activity and that PRE3 has peptidylglutamyl peptide hydrolytic specificity. Other β-type subunits are processed to an intermediate form, indicating that an additional nonspecific endopeptidase activity may exist which is important for peptide hydrolysis and for the generation of ligands for class I molecules of the major histocompatibility complex.

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References

  1. Emori, Y. et al. Mol. Cell. Biol. 11, 344–353 (1991).

    Article  CAS  Google Scholar 

  2. Rivett, A. J. Biochem. J. 291, 1–10 (1993).

    Article  CAS  Google Scholar 

  3. Peters, J.-M. Trends Biochem. Sci. 19, 377–382 (1994).

    Article  CAS  Google Scholar 

  4. Goldberg, A. L., Stein, R. & Adams, J. Chem. Biol. 2, 503–508 (1995).

    Article  CAS  Google Scholar 

  5. Hochstrasser, M. Curr. Opin. Cell Biol. 7, 215–223 (1995).

    Article  CAS  Google Scholar 

  6. Rubin, D. M. & Finley, D. Curr. Biol. 5, 854–858 (1995).

    Article  CAS  Google Scholar 

  7. Lord, M. Curr. Biol. 6, 1067–1069 (1996).

    Article  CAS  Google Scholar 

  8. Coux, O., Tanaka, K. & Goldberg, A. L. Annu. Rev. Biochem. 65, 801–847 (1996).

    Article  CAS  Google Scholar 

  9. Stock, D. et al. Curr. Opin. Biotech. 7, 376–385 (1996).

    Article  CAS  Google Scholar 

  10. Stock, D., Ditzel, L., Baumeister, W., Huber, R. & Löwe, J. Cold Spring Harbor Symp. Quant. Biol. LX, 525–532 (1995).

    Article  Google Scholar 

  11. Chen, P. & Hochstrasser, M. EMBO J. 14, 2620–2630 (1995).

    Article  CAS  Google Scholar 

  12. Groettrup, M., Soza, A., Kuckelkorn, U. & Kloetzel, P. M. Immunol. Today 17, 429–435 (1996).

    Article  CAS  Google Scholar 

  13. Hilt, W. & Wolf, D. H. Trends Biochem. Sci. 21, 96–102 (1996).

    Article  CAS  Google Scholar 

  14. Löwe, J. et al. Science 268, 533–539 (1995).

    Article  ADS  Google Scholar 

  15. Seemüller, E. et al. Science 268, 579–582 (1995).

    Article  ADS  Google Scholar 

  16. Brannigan, J. A. et al. Nature 378, 416–419 (1995).

    Article  ADS  CAS  Google Scholar 

  17. Heinemeyer, W., Tröndle, N., Albrecht, G. & Wolf, D. H. Biochemistry 33, 12229–12237 (1994).

    Article  CAS  Google Scholar 

  18. Ehring, B., Meyer, T. H., Eckerskorn, C., Lottspeich, F. & Tampé, R. Eur. J. Biochem. 235, 404–415 (1996).

    Article  CAS  Google Scholar 

  19. Dick, L. R. et al. Immunology 152, 3884–3894 (1994).

    CAS  Google Scholar 

  20. Wenzel, T., Eckerskorn, C., Lottspeich, F. & Baumeister, W. FEBS Lett. 349, 205–209 (1994).

    Article  CAS  Google Scholar 

  21. Kuckelkorn, U. et al. Eur. J. Immunol. 25, 2605–2611 (1995).

    Article  CAS  Google Scholar 

  22. Frentzel, S., Pesold-Hurt, B., Seelig, A. & Kloetzel, P.-M. J. Mol. Biol. 236, 975–981 (1994).

    Article  CAS  Google Scholar 

  23. Cerundolo, V., Kelly, A., Elliott, T., Trowsdale, J. & Townsend, A. Eur. J. Immunol. 25, 554–562 (1995).

    Article  CAS  Google Scholar 

  24. Seemüller, E., Lupas, A. & Baumeister, W. Nature 382, 468–470 (1996).

    Article  ADS  Google Scholar 

  25. Chen, P. & Hochstrasser, M. Cell 86, 961–972 (1996).

    Article  CAS  Google Scholar 

  26. Kopp, F. et al. J. Mol. Biol. 248, 264–272 (1995).

    CAS  PubMed  Google Scholar 

  27. Gaczynska, M., Rock, K. L. & Goldberg, A. L. Nature 365, 264–267 (1993).

    Article  ADS  CAS  Google Scholar 

  28. Driscoll, J., Brown, M. G., Finley, D. & Monaco, J. J. Nature 365, 262–264 (1993).

    Article  ADS  CAS  Google Scholar 

  29. Fehling, H. J. et al. Science 265, 1234–1237 (1994).

    Article  ADS  CAS  Google Scholar 

  30. Van Kaer, L. et al. Immunity 1, 533–541 (1994).

    Article  CAS  Google Scholar 

  31. Duggleby, H. J. et al. Nature 373, 264–268 (1995).

    Article  ADS  CAS  Google Scholar 

  32. Fenteany, G. et al. Science 268, 726–730 (1995).

    Article  ADS  CAS  Google Scholar 

  33. Heinemeyer, W., Gruhler, A., Möhrle, V., Mahé, Y. & Wolf, D. H. J. Biol. Chem. 268, 5115–5120 (1993).

    CAS  PubMed  Google Scholar 

  34. Hilt, W., Enenkel, C., Gruhler, A., Singer, T. & Wolf, D. H. J. Biol. Chem. 268, 3479–3486 (1993).

    CAS  PubMed  Google Scholar 

  35. Schmidtke, G. et al. EMBO J. 15, 6887–6898 (1996).

    Article  CAS  Google Scholar 

  36. Dick, L. R., Moomaw, R., DeMartino, G. N. & Slaughter, C. A. Biochemistry 30, 2725–2734 (1991).

    Article  CAS  Google Scholar 

  37. Hoffman, L. & Rechsteiner, M. J. Biol. Chem. 269, 16890–16895 (1994).

    CAS  PubMed  Google Scholar 

  38. Kania, M. A., DeMartino, G. N., Baumeister, W. & Goldberg, A. L. Eur. J. Biochem. 236, 510–516 (1996).

    Article  CAS  Google Scholar 

  39. Gray, C. W., Slaughter, C. A. & DeMartino, G. N. J. Mol. Biol. 236, 7–15 (1994).

    Article  CAS  Google Scholar 

  40. York, I. A. & Rock, K. L. Annu. Rev. Immunol. 14, 369–396 (1996).

    Article  CAS  Google Scholar 

  41. Niedermann, G. et al. Proc. Natl Acad. Sci. USA 93, 8572–8577 (1996).

    Article  ADS  CAS  Google Scholar 

  42. Rock, K. L. et al. Cell 78, 761–771 (1994).

    Article  CAS  Google Scholar 

  43. Sibille, C. et al. Curr. Biol. 5, 923–930 (1995).

    Article  CAS  Google Scholar 

  44. v. Engelhard, H. Curr. Opin. Immunol. 6, 13–23 (1994).

    Article  Google Scholar 

  45. Stohwasser, R., Kuckelkorn, U., Kraft, R., Kostka, S. & Kloetzel, P.-M. FEBS Lett. 383, 109–113 (1996).

    Article  CAS  Google Scholar 

  46. Madden, D. R., Gorga, J. C., Strominger, J. L. & Wiley, D. C. Nature 353, 321–325 (1991).

    Article  ADS  CAS  Google Scholar 

  47. Achstatter, T., Ehmann, C., Osaki, A. & Wolf, D. H. J. Biol. Chem. 259, 13344–13348 (1994).

    Google Scholar 

  48. Leslie, A. G. W. Collaborative Computational Project No. 4. Acta Crystallogr. D 50, 760–763 (1994).

    Article  Google Scholar 

  49. Navaza, J. Acta Crystallogr. A 50, 157–163 (1994).

    Article  Google Scholar 

  50. Turk, D. Thesis, Technische Univ., München (1992).

  51. Brunger, A. X-PLOR Version 3.1. A System for X-Ray Crystallography and NMR (1992).

    Google Scholar 

  52. Jones, T. A. J. Appl. Cryst. 11, 268–272 (1978).

    Article  CAS  Google Scholar 

  53. Engh, R. A. & Huber, R. Acta. Crystallogr. A 47, 392–400 (1991).

    Article  Google Scholar 

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

    Article  Google Scholar 

  55. Nicholls, A., Bharadwaj, R. & Honig, B. Biophys. J. 64, A166 (1993).

    Google Scholar 

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Author notes

  1. Jan Löwe & Daniela Stock

    Present address: MRC Laboratory of Molecular Biology, Hills Road, Cambridge, CB2 2QH, UK

Authors and Affiliations

  1. Max-Planck-Institut für Biochemie, D-82152, Martinsried, Germany

    Robert Huber

  2. Arbeitsgruppen für strukturelle Molekularbiologie der Max-Planck-Gesellschaft, Notkestr. 85, D-22603, Hamburg, Germany

    Hans D. Bartunik

Authors
  1. Michael Groll
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  2. Lars Ditzel
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  3. Jan Löwe
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  4. Daniela Stock
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  5. Matthias Bochtler
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  6. Hans D. Bartunik
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  7. Robert Huber
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Groll, M., Ditzel, L., Löwe, J. et al. Structure of 20S proteasome from yeast at 2.4Å resolution. Nature 386, 463–471 (1997). https://doi.org/10.1038/386463a0

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