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Switch-based mechanism of kinesin motors

Nature volume 411, pages 439–445 (2001)Cite this article

Abstract

Kinesin motors are specialized enzymes that use hydrolysis of ATP to generate force and movement along their cellular tracks, the microtubules. Although numerous biochemical and biophysical studies have accumulated much data that link microtubule-assisted ATP hydrolysis to kinesin motion, the structural view of kinesin movement remains unclear. This study of the monomeric kinesin motor KIF1A combines X-ray crystallography and cryo-electron microscopy, and allows analysis of force-generating conformational changes at atomic resolution. The motor is revealed in its two functionally critical states—complexed with ADP and with a non-hydrolysable analogue of ATP. The conformational change observed between the ADP-bound and the ATP-like structures of the KIF1A catalytic core is modular, extends to all kinesins and is similar to the conformational change used by myosin motors and G proteins. Docking of the ADP-bound and ATP-like crystallographic models of KIF1A into the corresponding cryo-electron microscopy maps suggests a rationale for the plus-end directional bias associated with the kinesin catalytic core.

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Figure 1: Structural analysis of KIF1A in the ADP and ATP-like states.
Figure 2: Nucleotide-dependent movements of the mechanical elements of kinesin motors.
Figure 3: Cryo-EM maps of the microtubules decorated by the KIF1A.
Figure 4: Interactions of KIF1A with the microtubule.
Figure 5: Models for motility by various kinesin motors.

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Acknowledgements

We thank C. Sindelar and J. Turner for providing comments on this manuscript and sharing their results before publication. We also thank M. Sugaya for technical assistance. This work was supported by a Center of Excellence Grant-in-aid from the Ministry of Education, Science, Sports, and Culture of Japan (N.H.), and by funding from an NIH program project grant.

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Author notes

  1. Masahide Kikkawa, Elena P. Sablin and Robert J. Fletterick: These authors contributed equally to this work

Authors and Affiliations

  1. Department of Cell Biology and Anatomy, Graduate School of Medicine, University of Tokyo, 7-3-1 Hongo Bunkyo-ku, 113-0033, Tokyo, Japan

    Masahide Kikkawa, Yasushi Okada, Hiroaki Yajima & Nobutaka Hirokawa

  2. Department of Biochemistry/Biophysics, University of California, San Francisco, 94143-0448, California, USA

    Elena P. Sablin & Robert J. Fletterick

Authors
  1. Masahide Kikkawa
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Corresponding author

Correspondence to Nobutaka Hirokawa.

Supplementary information

Figure 1 (GIF 8.9 KB)

Effective resolution of the cryo-EM maps. Fourier shell correlations between the two independent data sets are plotted. For the final map, the correlation coefficient fell to 0.5 at a resolution of 22 Å and 15 Å for the C351-ADP-microtubule complex and the C351-AMPPNP-microtubule complex, respectively.

Figure 2 (GIF 54.6 KB)

View showing electron density in the vicinity of the bound AMPPCP from a composite omit map (20 – 2.0 Å) contoured at 1.5 σ. A fragment of the final refined ATP-like KIF1A structure is shown. The γ-phosphate and Mg2+ ion (yellow asterisk) are labeled. The red asterisks indicate water molecules.

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Kikkawa, M., Sablin, E., Okada, Y. et al. Switch-based mechanism of kinesin motors. Nature 411, 439–445 (2001). https://doi.org/10.1038/35078000

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