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Processivity of the single-headed kinesin KIF1A through biased binding to tubulin


Conventional isoforms of the motor protein kinesin behave functionally not as ‘single molecules’ but as ‘two molecules’ paired. This dimeric structure poses a barrier to solving its mechanism1,2,3,4. To overcome this problem, we used an unconventional kinesin KIF1A (refs 5, 6) as a model molecule. KIF1A moves processively as an independent monomer7,8, and can also work synergistically as a functional dimer9. Here we show, by measuring its movement with an optical trapping system10, that a single ATP hydrolysis triggers a single stepping movement of a single KIF1A monomer. The step size is distributed stochastically around multiples of 8 nm with a gaussian-like envelope and a standard deviation of 15 nm. On average, the step is directional to the microtubule's plus-end against a load force of up to 0.15 pN. As the source for this directional movement, we show that KIF1A moves to the microtubule's plus-end by 3 nm on average on binding to the microtubule, presumably by preferential binding to tubulin on the plus-end side. We propose a simple physical formulation to explain the movement of KIF1A.

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Figure 1: Movement of KIF1A beads.
Figure 2: Stepping movement of KIF1A beads.
Figure 3: Plus-end-directed movement after binding to the microtubule.


  1. Hua, W., Chung, J. & Gelles, J. Distinguishing inchworm and hand-over-hand processive kinesin movement by neck rotation measurements. Science 295, 844–848 (2002)

    ADS  CAS  Article  Google Scholar 

  2. Kaseda, K., Higuchi, H. & Hirose, K. Coordination of kinesin's two heads studied with mutant heterodimers. Proc. Natl Acad. Sci. USA 99, 16058–16063 (2002)

    ADS  CAS  Article  Google Scholar 

  3. Rice, S. et al. A structural change in the kinesin motor protein that drives motility. Nature 402, 778–784 (1999)

    ADS  CAS  Article  Google Scholar 

  4. Gilbert, S. P., Moyer, M. L. & Johnson, K. A. Alternating site mechanism of the kinesin ATPase. Biochemistry 37, 792–799 (1998)

    CAS  Article  Google Scholar 

  5. Okada, Y., Yamazaki, H., Sekine Aizawa, Y. & Hirokawa, N. The neuron-specific kinesin superfamily protein KIF1A is a unique monomeric motor for anterograde axonal transport of synaptic vesicle precursors. Cell 81, 769–780 (1995)

    CAS  Article  Google Scholar 

  6. Hirokawa, N. Kinesin and dynein superfamily proteins and the mechanism of organelle transport. Science 279, 519–526 (1998)

    ADS  CAS  Article  Google Scholar 

  7. Okada, Y. & Hirokawa, N. Mechanism of the single-headed processivity: diffusional anchoring between the K-loop of kinesin and the C terminus of tubulin. Proc. Natl Acad. Sci. USA 97, 640–645 (2000)

    ADS  CAS  Article  Google Scholar 

  8. Okada, Y. & Hirokawa, N. A processive single-headed motor: Kinesin superfamily protein KIF1A. Science 283, 1152–1157 (1999)

    ADS  CAS  Article  Google Scholar 

  9. Tomishige, M., Klopfenstein, D. R. & Vale, R. D. Conversion of Unc104/KIF1A kinesin into a processive motor after dimerization. Science 297, 2263–2267 (2002)

    ADS  CAS  Article  Google Scholar 

  10. Nishiyama, M., Muto, E., Inoue, Y., Yanagida, T. & Higuchi, H. Substeps within the 8-nm step of the ATPase cycle of single kinesin molecules. Nature Cell Biol. 3, 425–428 (2001)

    CAS  Article  Google Scholar 

  11. Nishiyama, M., Higuchi, H. & Yanagida, T. Chemomechanical coupling of the forward and backward steps of single kinesin molecules. Nature Cell Biol. 4, 790–797 (2002)

    CAS  Article  Google Scholar 

  12. Kikkawa, M. et al. Switch-based mechanism of kinesin motors. Nature 411, 439–445 (2001)

    ADS  CAS  Article  Google Scholar 

  13. Block, S. M., Goldstein, L. S. & Schnapp, B. J. Bead movement by single kinesin molecules studied with optical tweezers. Nature 348, 348–352 (1990)

    ADS  CAS  Article  Google Scholar 

  14. Endow, S. A. & Higuchi, H. A mutant of the motor protein kinesin that moves in both directions on microtubules. Nature 406, 913–916 (2000)

    ADS  CAS  Article  Google Scholar 

  15. Svoboda, K., Schmidt, C. F., Schnapp, B. J. & Block, S. M. Direct observation of kinesin stepping by optical trapping interferometry. Nature 365, 721–727 (1993)

    ADS  CAS  Article  Google Scholar 

  16. Kikkawa, M., Okada, Y. & Hirokawa, N. 15 Å resolution model of the monomeric kinesin motor, KIF1A. Cell 100, 241–252 (2000)

    CAS  Article  Google Scholar 

  17. Veigel, C. et al. The motor protein myosin-I produces its working stroke in two steps. Nature 398, 530–533 (1999)

    ADS  CAS  Article  Google Scholar 

  18. Hackney, D. D. Pathway of ADP-stimulated ADP release and dissociation of tethered kinesin from microtubules. Implications for the extent of processivity. Biochemistry 41, 4437–4446 (2002)

    CAS  Article  Google Scholar 

  19. Astumian, R. D. Thermodynamics and kinetics of a Brownian motor. Science 276, 917–922 (1997)

    CAS  Article  Google Scholar 

  20. Julicher, F., Ajdari, A. & Prost, J. Modeling molecular motors. Rev. Mod. Phys. 69, 1269–1281 (1997)

    ADS  CAS  Article  Google Scholar 

  21. Farrell, C. M., Mackey, A. T., Klumpp, L. M. & Gilbert, S. P. The role of ATP hydrolysis for kinesin processivity. J. Biol. Chem. 277, 17079–17087 (2002)

    CAS  Article  Google Scholar 

  22. Berliner, E., Young, E. C., Anderson, K., Mahtani, H. K. & Gelles, J. Failure of a single-headed kinesin to track parallel to microtubule protofilaments. Nature 373, 718–721 (1995)

    ADS  CAS  Article  Google Scholar 

  23. Inoue, Y. et al. Movements of truncated kinesin fragments with a short or an artificial flexible neck. Proc. Natl Acad. Sci. USA 94, 7275–7280 (1997)

    ADS  CAS  Article  Google Scholar 

  24. Howard, J. & Hyman, A. A. Preparation of marked microtubules for the assay of the polarity of microtubule-based motors by fluorescence microscopy. Methods Cell Biol. 39, 105–113 (1993)

    CAS  Article  Google Scholar 

  25. deCastro, M. J., Fondecave, R. M., Clarke, L. A., Schmidt, C. F. & Stewart, R. J. Working strokes by single molecules of the kinesin-related microtubule motor ncd. Nature Cell Biol. 2, 724–729 (2000)

    CAS  Article  Google Scholar 

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We thank T. J. Mitchison for the gift of GMPCPP; H. Fukuda, H. Sato and M. Sugaya for technical and secretarial assistance; and J. Howard, M. Kikkawa and our colleagues for discussion. This work was supported by a Center of Excellence Grant-in-Aid (N.H.) and a Grant-in-Aid (H.H.) from the Ministry of Education, Culture, Sports, Science and Technology of Japan.

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Correspondence to Nobutaka Hirokawa.

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Okada, Y., Higuchi, H. & Hirokawa, N. Processivity of the single-headed kinesin KIF1A through biased binding to tubulin. Nature 424, 574–577 (2003).

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