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The gated gait of the processive molecular motor, myosin V

Nature Cell Biology volume 4, pages 59–65 (2002)Cite this article

Abstract

Class V myosins are actin-based molecular motors involved in vesicular and organellar transport. Single myosin V molecules move processively along F-actin, taking several 36-nm steps for each diffusional encounter. Here we have measured the mechanical interactions between mouse brain myosin V and rabbit skeletal F-actin. The working stroke produced by a myosin V head is ∼25 nm, consisting of two separate mechanical phases (20 + 5 nm). We show that there are preferred myosin binding positions (target zones) every 36 nm along the actin filament, and propose that the 36-nm steps of the double-headed motor are a combination of the working stroke (25 nm) of the bound head and a biased, thermally driven diffusive movement (11 nm) of the free head onto the next target zone. The second phase of the working stroke (5 nm) acts as a gate — like an escapement in a clock, coordinating the ATPase cycles of the two myosin V heads. This mechanism increases processivity and enables a single myosin V molecule to travel distances of several hundred nanometres along the actin filament.

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Figure 1: Duty-cycle ratio of myosin V.
Figure 2: Single-molecule mechanical interactions measured for MVS1.
Figure 3: Single-molecule mechanical interactions measured for TPMV.
Figure 4: Actin scanning experiment.
Figure 5: Stiffness measurements with TPMV and a model for processive myosin movement.

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References

  1. Reck-Peterson, S., Provance, D. W., Mooseker, M. S. & Mercer, J. A. Review: class V myosins. Biochim. Biophys. Acta 1496, 36–51 (2000).

    Article  CAS  Google Scholar 

  2. Cheney, R. E. et al. Brain myosin V is a two-headed unconventional myosin with motor activity. Cell 75, 13–23 (1993).

    Article  CAS  Google Scholar 

  3. Sellers, J. R. Myosins (Oxford Univ Press, 1999).

    Google Scholar 

  4. Miller, K. E. & Sheetz, M. P. Characterization of myosin V binding to brain vesicles. J. Biol. Chem. 275, 2598–2606 (2000).

    Article  CAS  Google Scholar 

  5. Mehta, A. D. et al. Myosin V is a processive actin-based motor. Nature 400, 590–593 (1999).

    Article  CAS  Google Scholar 

  6. Rief, M. et al. Myosin V stepping kinetics: a molecular model for processivity. Proc. Natl Acad. Sci. USA 97, 9482–9486 (2000).

    Article  CAS  Google Scholar 

  7. Sakamoto, T. I., Amitani, E., Yokota & Ando, T. Direct observation of processive movement by individual myosin V molecules. Biochem. Biophys. Res. Commun. 272, 586–590 (2000).

    Article  CAS  Google Scholar 

  8. Walker, M. et al. Two-headed binding of a processive myosin to F-actin. Nature 405, 804–807 (2000).

    Article  CAS  Google Scholar 

  9. De La Cruz, E. M., Wells, A. L., Rosenfeld, S. S., Ostap, E. M. & Sweeney, H. L. The kinetic mechanism of myosin V. Proc. Natl Acad. Sci. USA 96, 13726–13731 (1999).

    Article  CAS  Google Scholar 

  10. Schnitzer, M. J. & Block, S. M. Statistical kinetics of processive enzymes. Cold Spring Harb. Symp. Quant. Biol. 60, 793–802 (1995).

    Article  CAS  Google Scholar 

  11. Molloy, J. E. et al. Single molecule mechanics of heavy meromyosin and S1 interacting with rabbit or Drosophila actins using optical tweezers. Biophys. J. 68, 298s–305s (1995).

    CAS  PubMed  PubMed Central  Google Scholar 

  12. Wang, F. et al. Effect of ADP and ionic strength on the kinetic and motile properties of recombinant mouse myosin V. J. Biol. Chem. 275, 4329–4335 (2000).

    Article  CAS  Google Scholar 

  13. Cheney, R. E. Purification and assay of myosin V. Methods Enzymol. 298, 3–18 (1998).

    Article  CAS  Google Scholar 

  14. Veigel, C., Bartoo, M. L., White, D. C. S., Sparrow, J. C. & Molloy, J. E. The stiffness of rabbit skeletal, acto-myosin crossbridges determined with an optical tweezers transducer. Biophys. J. 75, 1424–1438 (1998).

    Article  CAS  Google Scholar 

  15. Molloy, J. E., Burns, J. E., Kendrick-Jones, J., Tregear, R. T. & White, D. C. S. Movement and force produced by a single myosin head. Nature 378, 209–212 (1995).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  17. Wray, J. Filament geometry and the activation of insect flight muscles. Nature 280, 325–326 (1979).

    Article  Google Scholar 

  18. Kramers, H. A. Brownian motion in a field of force and the diffusion model of chemical reactions. Physica 7, 284–304 (1940).

    Article  CAS  Google Scholar 

  19. Howard, J. Mechanics of Motor Proteins and the Cytoskeleton (Sinauer Associates, Sunderland, Massachusetts, 2001).

    Google Scholar 

  20. Berger, C. E.M, Fagnant, P. M., Heizmann, S., Trybus, K. M. & Geeves, M. A. ADP binding induces and asymmetry between the heads of unphosphorylated myosin. J. Biol. Chem. 276, 23240–23245 (2001).

    Article  CAS  Google Scholar 

  21. Rao, A. & Craig, A. M. (2000). Signaling between the actin cytoskeleton and the postsynaptic density of dendritic spines. Hippocampus 10, 527–541 (2000).

    Article  CAS  Google Scholar 

  22. Huxley, A. F. (1957). Muscle structure and theories of contraction. Progr. Biophys. Biophys. Chem. 7, 255–318 (1957).

    Article  CAS  Google Scholar 

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Acknowledgements

We thank E. Harvey for technical assistance, J. A. Hammer III for kindly supplying the MV clone, J. C. Sparrow, D. C. S. White, R. S. Adelstein, J. Trinick, P. J. Knight and E. Homsher for critical reading of the manuscript, and BBSRC, the Royal Society, the Wellcome Trust and the NIH for grant support.

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Authors and Affiliations

  1. Department of Biology, University of York, PO Box 373, York, YO10 5YW, UK

    Claudia Veigel, Marc L. Bartoo & Justin E. Molloy

  2. Laboratory of Molecular Cardiology, National Heart, Lung and Blood Institute, NIH, Bethesda, 20892, MD, USA

    Fei Wang & James R. Sellers

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  1. Claudia Veigel
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  2. Fei Wang
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  3. Marc L. Bartoo
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Correspondence to Claudia Veigel or James R. Sellers.

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Veigel, C., Wang, F., Bartoo, M. et al. The gated gait of the processive molecular motor, myosin V. Nat Cell Biol 4, 59–65 (2002). https://doi.org/10.1038/ncb732

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