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Crystal structure of the kinesin motor domain reveals a structural similarity to myosin

Abstract

KINESIN is the founding member of a superfamily of microtubule-based motor proteins that perform force-generating tasks such as organelle transport and chromosome segregation1,2. It has two identical 960-amino-acid chains containing an ammo-terminal globular motor domain, a central α-helical region that enables dimer formation through a coiled-coil, and a carboxy-terminal tail domain that binds light chains and possibly an organelle receptor1. The kinesin motor domain of 340 amino acids, which can produce movement in vitro3, is much smaller than that of myosin (850 amino acids) and dynein (1,000 amino acids), and is the smallest known molecular motor. Here, we report the crystal structure of the human kinesin motor domain with bound ADP determined to 1.8-Å resolution by X-ray crystallography. The motor consists primarily of a single α/β arrowhead-shaped domain with dimensions of 70×45×45 Å. Unexpectedly, it has a striking structural similarity to the core of the catalytic domain of the actin-based motor myosin. Although kinesin and myosin have virtually no amino-acid sequence identity, and exhibit distinct enzymatic4–6 and motile7–10 properties, our results suggest that these two classes of mechanochemical enzymes evolved from a common ancestor and share a similar force-generating strategy.

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References

  1. Bloom, G. & Endow, S. Motor Proteins 1: Kinesin (Academic, London, 1994).

    Google Scholar 

  2. Goldstein, L. S. A. Rev. Genet. 27, 319–351 (1993).

    Article  CAS  Google Scholar 

  3. Yang, J. T., Saxton, W. M., Stewart, R. J., Raff, E. C. & Goldstein, L. S. Science 249, 42–47 (1990).

    Article  ADS  CAS  Google Scholar 

  4. Hackney, D. D. Proc. natn. Acad. Sci. U.S.A. 85, 6314–6318 (1988).

    Article  ADS  CAS  Google Scholar 

  5. Gilbert, S. P., Webb, M. R., Brune, M. & Johnson, K. A. Nature 373, 671–676 (1995).

    Article  ADS  CAS  Google Scholar 

  6. Ma, Y. Z. & Taylor, E. W. Biochemistry 34, 13233–13241 (1995).

    Article  CAS  Google Scholar 

  7. Howard, J., Hudspeth, A. J. & Vale, R. D. Nature 342, 154–158 (1989).

    Article  ADS  CAS  Google Scholar 

  8. Block, S. M., Goldstein, L. S. & Schnapp, B. J. Nature 348, 348–352 (1990).

    Article  ADS  CAS  Google Scholar 

  9. Svoboda, K., Schmidt, C. F., Schnapp, B. J. & Block, S. M. Naqture 365, 721–727 (1993).

    ADS  CAS  Google Scholar 

  10. Coppin, C. M., Finer, J. T., Spudich, J. A. & Vale, R. D. Proc. natn. Acad. Sci. U.S.A. (in the press).

  11. Story, R. M. & Steitz, T. A. Nature 355, 374–376 (1992).

    Article  ADS  CAS  Google Scholar 

  12. Holm, L. & Sander, C. J. molec. Biol. 233, 123–138 (1993).

    Article  CAS  Google Scholar 

  13. Bagshaw, C. R. & Trentham, D. R. Biochem. J. 141, 331–349 (1974).

    Article  CAS  Google Scholar 

  14. Grammar, J. C., Kuwayama, H. & Yount, R. G. Biochemistry 32, 5752–5732 (1993).

    Article  Google Scholar 

  15. Fisher, A. J. et al. Biochemistry 34, 8960–8972 (1995).

    Article  CAS  Google Scholar 

  16. Taylor, E. W. in The Heart and Cardiovascular System (ed. Fozzard, H. A.) 1281–1293 (Raven, New York, 1992).

    Google Scholar 

  17. Yount, R. G., Cremo, C. R., Grammar, J. C. & Kerwin, B. A. Phil. Trans. R. Soc. Lend. B 336, 55–61 (1992).

    Article  ADS  CAS  Google Scholar 

  18. Sablin, E. P., Kull, F. J., Cooke, R., Vale, R. D. & Fletterick, R. J. Nature 380, 555–559 (1996).

    Article  ADS  CAS  Google Scholar 

  19. Whittaker, M. et al. Nature 378, 748–751 (1996).

    Article  ADS  Google Scholar 

  20. Jontes, J. D., Wilson-Kubalek, E. M. & Milligan, R. A. Nature 378, 751–753 (1995).

    Article  ADS  CAS  Google Scholar 

  21. Peskin, C. S. & Oster, G. Biophys. J. 68, 202s–211s (1995).

    CAS  PubMed  PubMed Central  Google Scholar 

  22. Vale, R. D. et al. Nature 380, 451–453 (1996).

    Article  ADS  CAS  Google Scholar 

  23. Berliner, E., Young, E. C., Anderson, K., Mahtani, H. K. & Gelles, J. Nature 373, 718–721 (1995).

    Article  ADS  CAS  Google Scholar 

  24. Spudich, J. A. Nature 372, 515–518 (1994).

    Article  ADS  CAS  Google Scholar 

  25. Navone, F. et al. J. Cell Biol. 117, 1263–1275 (1992).

    Article  CAS  Google Scholar 

  26. Fujiwara, S., Kull, F. J., Sablin, E. P., Stone, D. B. & Mendelson, R. A. Biophys. J. 69, 1563–1568 (1995).

    Article  ADS  CAS  Google Scholar 

  27. Naber, N., Matuska, M., Sablin, E. P., Pate, E. & Cooke, R. Protein Sci. 4, 1824–1831 (1995).

    Article  CAS  Google Scholar 

  28. McRee, D. E. Practical Protein Crystallography (Academic, San Deigo, 1993).

    Google Scholar 

  29. Collaborative Computing Project No. 4 Acta crystallogr. D50, 760–763 (1994).

  30. Brunger, A. T. X-PLOR Version 3.1. A system forX-ray Crystallography and NMR (Yale Univ. Press, New Haven, CT, 1992).

    Google Scholar 

  31. Laskowski, R. A., MacArthur, M. W., Moss, D. S. & Thornton, J. M. J. appl. Crystallogr. 26, 283–291 (1993).

    Article  CAS  Google Scholar 

  32. Kraulis, P. J. J. appl. Crystallogr. 24, 946–950 (1991).

    Article  Google Scholar 

  33. Rayment, I. et al. Science 261, 58–65 (1993).

    Article  ADS  CAS  Google Scholar 

  34. Wells, J. A. & Yount, R. G. Proc. natn. Acad. Sci. U.S.A. 76, 4966–4970 (1979).

    Article  ADS  CAS  Google Scholar 

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Jon Kull, F., Sablin, E., Lau, R. et al. Crystal structure of the kinesin motor domain reveals a structural similarity to myosin. Nature 380, 550–555 (1996). https://doi.org/10.1038/380550a0

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