1. Structural Biology and Molecular Biophysics

High-resolution structures of kinesin on microtubules provide a basis for nucleotide-gated force generation

  1. Zhiguo Shang
  2. Kaifeng Zhou
  3. Chen Xu
  4. Roseann Csencsits
  5. Jared C Cochran
  6. Charles V Sindelar  Is a corresponding author
  1. Brandeis University, United States
  2. Yale University, United States
  3. Lawrence Berkeley National Laboratory, United States
  4. Indiana University, United States
https://doi.org/10.7554/eLife.04686
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  1. Zhiguo Shang
  2. Kaifeng Zhou
  3. Chen Xu
  4. Roseann Csencsits
  5. Jared C Cochran
  6. Charles V Sindelar
(2014)
High-resolution structures of kinesin on microtubules provide a basis for nucleotide-gated force generation
eLife 3:e04686.
https://doi.org/10.7554/eLife.04686
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Abstract

Microtubule-based transport by the kinesin motors, powered by ATP hydrolysis, is essential for a wide range of vital processes in eukaryotes. We obtained insight into this process by developing atomic models for no-nucleotide and ATP states of the monomeric kinesin motor domain on microtubules from cryo-EM reconstructions at 5-6Å resolution. By comparing these models with existing X-ray structures of ADP-bound kinesin, we infer a mechanistic scheme in which microtubule attachment, mediated by a universally conserved 'linchpin' residue in kinesin (N255), triggers a clamshell opening of the nucleotide cleft and accompanying release of ADP. Binding of ATP re-closes the cleft in a manner that tightly couples to translocation of cargo, via kinesin's 'neck linker' element. These structural transitions are reminiscent of the analogous nucleotide-exchange steps in the myosin and F1-ATPase motors, and inform how the two heads of a kinesin dimer 'gate' each other to promote coordinated stepping along microtubules.

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Author details

  1. Zhiguo Shang

    Brandeis University, Waltham, United States
    Competing interests
    The authors declare that no competing interests exist.

  2. Kaifeng Zhou

    Yale University, New Haven, United States
    Competing interests
    The authors declare that no competing interests exist.

  3. Chen Xu

    Brandeis University, Waltham, United States
    Competing interests
    The authors declare that no competing interests exist.

  4. Roseann Csencsits

    Lawrence Berkeley National Laboratory, Berkeley, United States
    Competing interests
    The authors declare that no competing interests exist.

  5. Jared C Cochran

    Indiana University, Bloomington, United States
    Competing interests
    The authors declare that no competing interests exist.

  6. Charles V Sindelar

    Yale University, New Haven, United States
    For correspondence
    charles.sindelar@yale.edu
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. Anthony A Hyman, Max Planck Institute of Molecular Cell Biology and Genetics, Germany

Version history

  1. Received: September 12, 2014
  2. Accepted: November 20, 2014
  3. Accepted Manuscript published: November 21, 2014 (version 1)
  4. Accepted Manuscript updated: November 28, 2014 (version 2)
  5. Version of Record published: December 24, 2014 (version 3)

Copyright

© 2014, Shang 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. Zhiguo Shang
  2. Kaifeng Zhou
  3. Chen Xu
  4. Roseann Csencsits
  5. Jared C Cochran
  6. Charles V Sindelar
(2014)
High-resolution structures of kinesin on microtubules provide a basis for nucleotide-gated force generation
eLife 3:e04686.
https://doi.org/10.7554/eLife.04686

Share this article

https://doi.org/10.7554/eLife.04686

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