1. Structural Biology and Molecular Biophysics

Structural basis of cooperativity in kinesin revealed by 3D reconstruction of a two-head-bound state on microtubules

  1. Daifei Liu
  2. Xueqi Liu
  3. Zhiguo Shang
  4. Charles Vaughn Sindelar  Is a corresponding author
  1. Yale University, United States
  2. University of Texas Southwestern Medical School, United States
https://doi.org/10.7554/eLife.24490
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  1. Daifei Liu
  2. Xueqi Liu
  3. Zhiguo Shang
  4. Charles Vaughn Sindelar
(2017)
Structural basis of cooperativity in kinesin revealed by 3D reconstruction of a two-head-bound state on microtubules
eLife 6:e24490.
https://doi.org/10.7554/eLife.24490
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Abstract

The detailed basis of walking by dimeric molecules of kinesin along microtubules has remained unclear, partly because available structural methods have been unable to capture microtubule-bound intermediates of this process. Utilizing novel electron cryomicroscopy methods, we solved structures of microtubule-attached, dimeric kinesin bound to an ATP analog. We find that under these conditions, the kinesin dimer can attach to the microtubule with either one or two motor domains, and we present sub-nanometer resolution reconstructions of both states. The former structure reveals a novel kinesin conformation that revises the current understanding of how ATP binding is coupled to forward stepping of the motor. The latter structure indicates how tension between the two motor domains keeps their cycles out of phase in order to stimulate directional motility. The methods presented here pave the way for future structural studies of a variety of challenging macromolecules that bind to microtubules and other filaments.

Data availability

The following data sets were generated
    1. Liu D
    2. Liu X
    3. Shang Z
    4. Sindelar CV
    (2017) Dimeric Kinesin-1 on Microtubules with ADP-AlFx
    Publicly available at the Electron Microscopy Data Bank (accession no. EMD-8546).
    http://emsearch.rutgers.edu/atlas/8546_summary.html

Article and author information

Author details

  1. Daifei Liu

    Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, United States
    Competing interests
    The authors declare that no competing interests exist.

  2. Xueqi Liu

    Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, United States
    Competing interests
    The authors declare that no competing interests exist.

  3. Zhiguo Shang

    Departments of Cell Biology and Biophysics, University of Texas Southwestern Medical School, Dallas, United States
    Competing interests
    The authors declare that no competing interests exist.

  4. Charles Vaughn Sindelar

    Department of Molecular Biophysics and Biochemistry, Yale University, New Haven, United States
    For correspondence
    charles.sindelar@yale.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6646-7776

Funding

American Cancer Society (ACS-IRG-58-012-55)

  • Charles Vaughn Sindelar

National Institutes of Health (R01 GM 110530-01)

  • Charles Vaughn Sindelar

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

Copyright

© 2017, Liu 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. Daifei Liu
  2. Xueqi Liu
  3. Zhiguo Shang
  4. Charles Vaughn Sindelar
(2017)
Structural basis of cooperativity in kinesin revealed by 3D reconstruction of a two-head-bound state on microtubules
eLife 6:e24490.
https://doi.org/10.7554/eLife.24490

Share this article

https://doi.org/10.7554/eLife.24490

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