Letter | Published:

Crystal structure of the APC10/DOC1 subunit of the human anaphase-promoting complex

Nature Structural Biology volume 8, pages 784788 (2001) | Download Citation

Subjects

Abstract

The anaphase-promoting complex (APC), or cyclosome, is a cell cycle-regulated ubiquitin ligase that controls progression through mitosis and the G1 phase of the cell cycle. The APC is composed of at least 11 subunits; no structure has been determined for any of these subunits. The subunit APC10/DOC1, a one-domain protein consisting of 185 amino acids, has a conserved core (residues 22–161) that is homologous to domains found in several other putative ubiquitin ligases and, therefore, may play a role in ubiquitination reactions. Here we report the crystal structure of human APC10 at 1.6 Å resolution. The core of the protein is formed by a β-sandwich that adopts a jellyroll fold. Unexpectedly, this structure is highly similar to ligand-binding domains of several bacterial and eukaryotic proteins, such as galactose oxidase and coagulation factor Va, raising the possibility that APC10 may function by binding a yet unidentified ligand. We further provide biochemical evidence that the C-terminus of APC10 binds to CDC27/APC3, an APC subunit that contains multiple tetratrico peptide repeats.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Accessions

Protein Data Bank

References

  1. 1.

    Exp. Cell Res. 248, 339–349 (1999).

  2. 2.

    , , , & Proc. Natl. Acad. Sci. USA 97, 8973–8978 (2000).

  3. 3.

    et al. Mol. Biol. Cell 11, 2315–2325 (2000).

  4. 4.

    & Mol. Biol. Cell 8, 1877–1887 (1997).

  5. 5.

    et al. Science 279, 1216–1219 (1998).

  6. 6.

    , & EMBO J. 17, 5388–5399 (1998).

  7. 7.

    et al. J. Biol. Chem. 274, 14500–14507 (1999).

  8. 8.

    & Genomics 72, 78–87 (2001).

  9. 9.

    , & Protoplasma 211, 20–28 (2000).

  10. 10.

    Nat. Rev. Mol. Cell Biol. 2, 169–178 (2001).

  11. 11.

    , , & J. Mol. Biol. 238, 794–814 (1994).

  12. 12.

    , & Structure 3, 1197–1205 (1995).

  13. 13.

    et al. Nature 402, 434–439 (1999).

  14. 14.

    et al. Nature Struct. Biol. 6, 884–893 (1999).

  15. 15.

    , , & Protein Sci. 7, 1626–1631 (1998).

  16. 16.

    et al. Cell 101, 199–210 (2000).

  17. 17.

    , , & Nature Struct. Biol. 7, 1091–1095 (2000).

  18. 18.

    , , , & Mol. Cell. 7, 907–913 (2001).

  19. 19.

    , & Gene 85, 109–114 (1989).

  20. 20.

    et al. Eur. J. Biochem. 230, 788–796 (1995).

  21. 21.

    & Methods Enzymol. 276, 307–326 (1997).

  22. 22.

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

  23. 23.

    In Joint CCP4 and ESD-EACBM Newsletter on Protein Crystallography 31, 34–38 (1994).

  24. 24.

    , , & . Acta Crystallogr. A 47, 110–119 (1991).

  25. 25.

    et al. Acta Crystallogr. D 54, 905–921 (1998).

  26. 26.

    , , , & J. Biomol. NMR 8, 477–486 (1996).

  27. 27.

    & J. Mol. Biol. 233, 123–138 (1993).

  28. 28.

    , , , & Nature 410, 116–120 (2001).

  29. 29.

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

  30. 30.

    & Acta Crystallogr. D 50, 869–873 (1994).

  31. 31.

    J. Mol. Graphics 15, 132–134 (1997).

  32. 32.

    , & Biophys. J. 64, A166 (1993).

  33. 33.

    Protein Eng. 6, 37–40 (1993).

Download references

Acknowledgements

The assistance of G.P. Bourenkov and H. Bartunik at DESY, Hamburg for data recording is greatly acknowledged. We thank K. Mechtler for peptide synthesis and M. Lachner for the histone H4 N-terminal peptide matrix. Research in the laboratory of J.-M. P. is supported by Boehringer Ingelheim and by grants from the Austrian Science Fund and the Austrian Industrial Research Promotion Fund.

Author information

Affiliations

  1. Max-Planck-Institut für Biochemie, Abteilung Strukturforschung, Am Klopferspitz 18a, D-82152 Martinsried, Germany.

    • Kerstin S. Wendt
    • , Uwe Jacob
    • , Robert Huber
    •  & Peter Sondermann
  2. Research Institute of Molecular Pathology, Dr.-Bohr Gasse 7, A-1030 Vienna, Austria.

    • Hartmut C. Vodermaier
    • , Christian Gieffers
    • , Michael Gmachl
    •  & Jan-Michael Peters
  3. Boehringer-Ingelheim Austria, Dr.-Boehringer-Gasse 5-11, A-1120 Vienna, Austria.

    • Michael Gmachl

Authors

  1. Search for Kerstin S. Wendt in:

  2. Search for Hartmut C. Vodermaier in:

  3. Search for Uwe Jacob in:

  4. Search for Christian Gieffers in:

  5. Search for Michael Gmachl in:

  6. Search for Jan-Michael Peters in:

  7. Search for Robert Huber in:

  8. Search for Peter Sondermann in:

Corresponding author

Correspondence to Kerstin S. Wendt.

About this article

Publication history

Received

Accepted

Published

DOI

https://doi.org/10.1038/nsb0901-784

Further reading