1. Biophysics and Structural Biology
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The divergent mitotic kinesin MKLP2 exhibits atypical structure and mechanochemistry

  1. Joseph Atherton
  2. I-Mei Yu
  3. Alexander Cook
  4. Joseph M Muretta
  5. Agnel Joseph
  6. Jennifer Major
  7. Yannick Sourigues
  8. Jeffrey Clause
  9. Maya Topf
  10. Steven S Rosenfeld
  11. Anne Houdusse
  12. Carolyn A Moores Is a corresponding author
  1. Birkbeck College, United Kingdom
  2. Institut Curie, Centre National de la Recherche Scientifique, France
  3. University of Minnesota, United States
  4. Lerner Research Institute, Cleveland Clinic, United States
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Cite as: eLife 2017;6:e27793 doi: 10.7554/eLife.27793

Abstract

MKLP2, a kinesin-6, has critical roles during the metaphase-anaphase transition and cytokinesis. Its motor domain contains conserved nucleotide binding motifs, but is divergent in sequence (~35% identity) and size (~40% larger) compared to other kinesins. Using cryo-electron microscopy and biophysical assays, we have undertaken a mechanochemical dissection of the microtubule-bound MKLP2 motor domain during its ATPase cycle, and show that many facets of its mechanism are distinct from other kinesins. While the MKLP2 neck-linker is directed towards the microtubule plus-end in an ATP-like state, it does not fully dock along the motor domain. Furthermore, the footprint of the MKLP2 motor domain on the MT surface is altered compared to motile kinesins, and enhanced by kinesin-6-specific sequences. The conformation of the highly extended loop6 insertion characteristic of kinesin-6s is nucleotide-independent and does not contact the MT surface. Our results emphasize the role of family-specific insertions in modulating kinesin motor function.

Article and author information

Author details

  1. Joseph Atherton

    Institute of Structural and Molecular Biology, Birkbeck College, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  2. I-Mei Yu

    Structural Motility, Institut Curie, Centre National de la Recherche Scientifique, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  3. Alexander Cook

    Institute of Structural and Molecular Biology, Birkbeck College, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  4. Joseph M Muretta

    Department of Biochemistry, Molecular Biology, and Biophysics, University of Minnesota, Minneapolis, United States
    Competing interests
    The authors declare that no competing interests exist.
  5. Agnel Joseph

    Institute of Structural and Molecular Biology, Birkbeck College, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  6. Jennifer Major

    Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Clevelan, United States
    Competing interests
    The authors declare that no competing interests exist.
  7. Yannick Sourigues

    Structural Motility, Institut Curie, Centre National de la Recherche Scientifique, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  8. Jeffrey Clause

    Structural Motility, Institut Curie, Centre National de la Recherche Scientifique, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  9. Maya Topf

    Institute of Structural and Molecular Biology, Birkbeck College, London, United Kingdom
    Competing interests
    The authors declare that no competing interests exist.
  10. Steven S Rosenfeld

    Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, United States
    Competing interests
    The authors declare that no competing interests exist.
  11. Anne Houdusse

    Structural Motility, Institut Curie, Centre National de la Recherche Scientifique, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  12. Carolyn A Moores

    Institute of Structural and Molecular Biology, Birkbeck College, London, United Kingdom
    For correspondence
    c.moores@mail.cryst.bbk.ac.uk
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon 0000-0001-5686-6290

Funding

Medical Research Council (MR/J000973/1)

  • Carolyn A Moores

Medical Research Council (MR/J003867/1)

  • Alexander Cook

Medical Research Council (MR/M019292/1)

  • Maya Topf

American Heart Association (SDG20480032)

  • Joseph M Muretta

National Institute of General Medical Sciences (GM102875 NS073610)

  • Steven S Rosenfeld

Centre National de la Recherche Scientifique

  • Anne Houdusse

Agence Nationale de la Recherche

  • Anne Houdusse

Ligue Contre le Cancer

  • Anne Houdusse

European Commission (Marie Curie Fellowship)

  • I-Mei Yu

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Edward H Egelman, Reviewing Editor, University of Virginia, United States

Publication history

  1. Received: April 15, 2017
  2. Accepted: August 7, 2017
  3. Accepted Manuscript published: August 11, 2017 (version 1)

Copyright

© 2017, Atherton 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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