1. Biochemistry and Chemical Biology
  2. Structural Biology and Molecular Biophysics
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TRIP13 is a protein-remodeling AAA+ ATPase that catalyzes MAD2 conformation switching

  1. Qiaozhen Ye
  2. Scott C Rosenberg
  3. Arne Moeller
  4. Jeffrey A Speir
  5. Tiffany Y Su
  6. Kevin D Corbett  Is a corresponding author
  1. Ludwig Institute for Cancer Research, San Diego Branch, United States
  2. The Scripps Research Institute, United States
Research Article
  • Cited 78
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Cite this article as: eLife 2015;4:e07367 doi: 10.7554/eLife.07367
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Abstract

The AAA+ family ATPase TRIP13 is a key regulator of meiotic recombination and the spindle assembly checkpoint, acting on signaling proteins of the conserved HORMA domain family. Here we present the structure of the C. elegans TRIP13 ortholog PCH-2, revealing a new family of AAA+ ATPase protein remodelers. PCH-2 possesses a substrate-recognition domain related to those of the protein remodelers NSF and p97, while its overall hexameric architecture and likely structural mechanism bear close similarities to the bacterial protein unfoldase ClpX. We find that TRIP13, aided by the adapter protein p31(comet), converts the HORMA-family spindle checkpoint protein MAD2 from a signaling-active 'closed' conformer to an inactive 'open' conformer. We propose that TRIP13 and p31(comet) collaborate to inactivate the spindle assembly checkpoint through MAD2 conformational conversion and disassembly of mitotic checkpoint complexes. A parallel HORMA protein disassembly activity likely underlies TRIP13's critical regulatory functions in meiotic chromosome structure and recombination.

Article and author information

Author details

  1. Qiaozhen Ye

    Ludwig Institute for Cancer Research, San Diego Branch, La Jolla, United States
    Competing interests
    The authors declare that no competing interests exist.
  2. Scott C Rosenberg

    Ludwig Institute for Cancer Research, San Diego Branch, La Jolla, United States
    Competing interests
    The authors declare that no competing interests exist.
  3. Arne Moeller

    National Resource for Automated Molecular Microscopy, Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, United States
    Competing interests
    The authors declare that no competing interests exist.
  4. Jeffrey A Speir

    National Resource for Automated Molecular Microscopy, Department of Integrative Structural and Computational Biology, The Scripps Research Institute, La Jolla, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Tiffany Y Su

    Ludwig Institute for Cancer Research, San Diego Branch, La Jolla, United States
    Competing interests
    The authors declare that no competing interests exist.
  6. Kevin D Corbett

    Ludwig Institute for Cancer Research, San Diego Branch, La Jolla, United States
    For correspondence
    kcorbett@ucsd.edu
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. Axel T Brunger, Stanford University, United States

Publication history

  1. Received: March 7, 2015
  2. Accepted: April 21, 2015
  3. Accepted Manuscript published: April 28, 2015 (version 1)
  4. Version of Record published: May 22, 2015 (version 2)

Copyright

© 2015, Ye et al.

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.

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  1. Further reading

Further reading

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