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

Nature Structural Biology volume 8, pages 784–788 (2001)Cite this article

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.

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Figure 1: Structure of human APC10.
Figure 2: The electrostatic surface potential, from negative (red) to positive (blue), is mapped on a solid surface representation of APC10.
Figure 3: Structurally and sequentially related proteins to human APC10.
Figure 4: Interaction of APC10 with TPR-containing APC subunits.

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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.

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Authors and Affiliations

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

    Kerstin S. Wendt, Uwe Jacob, Robert Huber & Peter Sondermann

  2. Research Institute of Molecular Pathology, Dr.-Bohr Gasse 7, Vienna, A-1030, Austria

    Hartmut C. Vodermaier, Christian Gieffers, Michael Gmachl & Jan-Michael Peters

  3. Boehringer-Ingelheim Austria, Dr.-Boehringer-Gasse 5-11, Vienna, A-1120, Austria

    Michael Gmachl

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  1. Kerstin S. Wendt
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Correspondence to Kerstin S. Wendt.

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Wendt, K., Vodermaier, H., Jacob, U. et al. Crystal structure of the APC10/DOC1 subunit of the human anaphase-promoting complex. Nat Struct Mol Biol 8, 784–788 (2001). https://doi.org/10.1038/nsb0901-784

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