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
Share this article
Cite this article
  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
  2. Download BibTeX
  3. Download .RIS

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.

Article and author information

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.

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.

Metrics

  • 5,682
    views
  • 795
    downloads
  • 144
    citations

Views, downloads and citations are aggregated across all versions of this paper published by eLife.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  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

Categories and tags

Research organism

Further reading

    1. Structural Biology and Molecular Biophysics

    Conserved mechanisms of microtubule-stimulated ADP release, ATP binding, and force generation in transport kinesins

    Joseph Atherton, Irene Farabella ... Carolyn A Moores
    Research Article Updated

    Kinesins are a superfamily of microtubule-based ATP-powered motors, important for multiple, essential cellular functions. How microtubule binding stimulates their ATPase and controls force generation is not understood. To address this fundamental question, we visualized microtubule-bound kinesin-1 and kinesin-3 motor domains at multiple steps in their ATPase cycles—including their nucleotide-free states—at ∼7 Å resolution using cryo-electron microscopy. In both motors, microtubule binding promotes ordered conformations of conserved loops that stimulate ADP release, enhance microtubule affinity and prime the catalytic site for ATP binding. ATP binding causes only small shifts of these nucleotide-coordinating loops but induces large conformational changes elsewhere that allow force generation and neck linker docking towards the microtubule plus end. Family-specific differences across the kinesin–microtubule interface account for the distinctive properties of each motor. Our data thus provide evidence for a conserved ATP-driven mechanism for kinesins and reveal the critical mechanistic contribution of the microtubule interface.