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The molecular architecture of the Dam1 kinetochore complex is defined by cross-linking based structural modelling

Author

Listed:
  • Alex Zelter

    (University of Washington)

  • Massimiliano Bonomi

    (University of Cambridge)

  • Jae ook Kim

    (University of Washington)

  • Neil T. Umbreit

    (University of Washington)

  • Michael R. Hoopmann

    (Institute for Systems Biology)

  • Richard Johnson

    (University of Washington)

  • Michael Riffle

    (University of Washington)

  • Daniel Jaschob

    (University of Washington)

  • Michael J. MacCoss

    (University of Washington)

  • Robert L. Moritz

    (Institute for Systems Biology)

  • Trisha N. Davis

    (University of Washington)

Abstract

Accurate segregation of chromosomes during cell division is essential. The Dam1 complex binds kinetochores to microtubules and its oligomerization is required to form strong attachments. It is a key target of Aurora B kinase, which destabilizes erroneous attachments allowing subsequent correction. Understanding the roles and regulation of the Dam1 complex requires structural information. Here we apply cross-linking/mass spectrometry and structural modelling to determine the molecular architecture of the Dam1 complex. We find microtubule attachment is accompanied by substantial conformational changes, with direct binding mediated by the carboxy termini of Dam1p and Duo1p. Aurora B phosphorylation of Dam1p C terminus weakens direct interaction with the microtubule. Furthermore, the Dam1p amino terminus forms an interaction interface between Dam1 complexes, which is also disrupted by phosphorylation. Our results demonstrate that Aurora B inhibits both direct interaction with the microtubule and oligomerization of the Dam1 complex to drive error correction during mitosis.

Suggested Citation

  • Alex Zelter & Massimiliano Bonomi & Jae ook Kim & Neil T. Umbreit & Michael R. Hoopmann & Richard Johnson & Michael Riffle & Daniel Jaschob & Michael J. MacCoss & Robert L. Moritz & Trisha N. Davis, 2015. "The molecular architecture of the Dam1 kinetochore complex is defined by cross-linking based structural modelling," Nature Communications, Nature, vol. 6(1), pages 1-12, December.
  • Handle: RePEc:nat:natcom:v:6:y:2015:i:1:d:10.1038_ncomms9673
    DOI: 10.1038/ncomms9673
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