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A structural change in the kinesin motor protein that drives motility

Nature volume 402, pages 778–784 (1999)Cite this article

Abstract

Kinesin motors power many motile processes by converting ATP energy into unidirectional motion along microtubules. The force-generating and enzymatic properties of conventional kinesin have been extensively studied; however, the structural basis of movement is unknown. Here we have detected and visualized a large conformational change of a ∼15-amino-acid region (the neck linker) in kinesin using electron paramagnetic resonance, fluorescence resonance energy transfer, pre-steady state kinetics and cryo-electron microscopy. This region becomes immobilized and extended towards the microtubule ‘plus’ end when kinesin binds microtubules and ATP, and reverts to a more mobile conformation when γ-phosphate is released after nucleotide hydrolysis. This conformational change explains both the direction of kinesin motion and processive movement by the kinesin dimer.

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Figure 1: Structure of the rat kinesin monomer25 (numbered as in human kinesin).
Figure 2: Electron paramagnetic resonance spectra for kinesin C333–MSL in several nucleotide states, both free in solution and bound to microtubules.
Figure 3: Nucleotide-dependent energy transfer between GFP (donor) at the end of the neck linker and tetramethylrhodamine (acceptor) at C220.
Figure 4: Three-dimensional and difference maps of gold labelled motors attached to microtubules calculated by cryo-EM and image analysis.
Figure 5: Models for motility by truncated kinesin monomers and processive dimers.

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Acknowledgements

We thank L. Sweeney for encouragement; A. Ruby for assistance with protein preparations; B. Sheehan for computing and image processing; and M. Tomishige for examining the processivity of cys-light K560–GFP. We thank R. Case and K. Thorn for comments on the manuscript. This work was supported, in part, by grants for the NIH (R.A.M., E.W.T., R.C. and R.D.V.), and the NSF (B.O.C.). S.R. is supported by the UCSF Graduate Group in Biophysics.

Author information

Authors and Affiliations

  1. The Howard Hughes Medical Institute,

    Cynthia L. Hart & Ronald D. Vale

  2. Departments of Cellular and Molecular Pharmacology,

    Sarah Rice & Ronald D. Vale

  3. Biochemistry and Biophysics, University of California, San Francisco, 94143, California, USA

    Nariman Naber & Roger Cooke

  4. Department of Cell Biology, The Scripps Research Institute, La Jolla, 92037, California, USA

    Abel W. Lin, Shane M. Cain, Elizabeth M. Wilson-Kubalek, Michael Whittaker & Ronald A. Milligan

  5. Department of Physiology, University of Pennsylvania School of Medicine, Philadelphia, 19104, Pennsylvania, USA

    Daniel Safer

  6. Department of Cell and Structural Biology, Beckman Institute, University of Illinois at Urbana-Champaign, Urbana-Champaign, 61801, Illinois, USA

    Bridget O. Carragher

  7. Department of Molecular Genetics and Cell Biology, University of Chicago, Chicago, 60637, Illinois, USA

    Elena Pechatnikova & Edwin W. Taylor

  8. Department of Pure and Applied Mathematics, Washington State University, Pullman, 99164, Washington, USA

    Edward Pate

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Correspondence to Ronald D. Vale.

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Rice, S., Lin, A., Safer, D. et al. A structural change in the kinesin motor protein that drives motility. Nature 402, 778–784 (1999). https://doi.org/10.1038/45483

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