Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Timeline
  • Published:

The myosin swinging cross-bridge model

Nature Reviews Molecular Cell Biology volume 2, pages 387–392 (2001)Cite this article

Abstract

No biological system has been studied by more diverse approaches than the actin-based molecular motor myosin. Biophysics, biochemistry, physiology, classical genetics and molecular genetics have all made their contributions, and myosin is now becoming one of the best-understood enzymes in biology.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: The swinging cross-bridge model.
Figure 2: Prestroke and poststroke states of subfragment 1.
Figure 3: The actin-activated myosin-II ATPase cycle.
Figure 4: Predicted structure of myosin V.
Figure 5: Experimental scheme of the force-feedback-enhanced laser trap.
Figure 6: Nucleotide-dependent processive stepping of myosin V along an actin filament.

References

  1. Huxley, H. E. The mechanism of muscular contraction. Science 164, 1356–1365 (1969).

    Article  CAS  Google Scholar 

  2. Huxley, A. F. & Simmons, R. M. Proposed mechanism of force generation in striated muscle. Nature 233, 533–538 (1971).

    Article  CAS  Google Scholar 

  3. Moore, P. B., Huxley, H. E. & de Rosier, D. J. Three-dimensional reconstruction of F-actin, thin filaments and decorated thin filaments. J. Mol. Biol. 50, 279–295 (1970).

    Article  CAS  Google Scholar 

  4. Lymn, R. W. & Taylor, E. W. Mechanism of adenosine triphosphate hydrolysis by actomyosin. Biochemistry 10, 4617–4624 (1971).

    Article  CAS  Google Scholar 

  5. Yount, R. G., Ojala, D. & Babcock, D. Interaction of P–N–P and P–C–P analogs of adenosine triphosphate with heavy meromyosin, myosin, and actomyosin. Biochemistry 10, 2490–2496 (1971).

    Article  CAS  Google Scholar 

  6. Goody, R. S. & Eckstein, F. Thiophosphate analogs of nucleoside di- and triphosphates. J. Am. Chem. Soc. 93, 6252–6257 (1971).

    Article  CAS  Google Scholar 

  7. Goody, R. S. & Hofmann, W. Stereochemical aspects of the interaction of myosin and actomyosin with nucleotides. J. Muscle Res. Cell Motil. 1, 101–115 (1980).

    Article  CAS  Google Scholar 

  8. Pollard, T. D. & Korn, E. D. Acanthamoeba myosin. I. Isolation from Acanthamoeba castellanii of an enzyme similar to muscle myosin. J. Biol. Chem. 248, 4682–4690 (1973).

    CAS  PubMed  Google Scholar 

  9. Huxley, H. E. et al. Time-resolved X-ray diffraction studies of the myosin layer-line reflections during muscle contraction. J. Mol. Biol. 158, 637–84 (1982).

    Article  CAS  Google Scholar 

  10. Sheetz, M. P. & Spudich, J. A. Movement of myosin-coated fluorescent beads on actin cables in vitro. Nature 303, 31–35 (1983).

    Article  CAS  Google Scholar 

  11. Vale, R. D., Reese, T. S. & Sheetz, M. P. Identification of a novel force-generating protein, kinesin, involved in microtubule-based motility. Cell 42, 39–50 (1985).

    Article  CAS  Google Scholar 

  12. Kron, S. J. & Spudich, J. A. Fluorescent actin filaments move on myosin fixed to a glass surface. Proc. Natl Acad. Sci. USA 83, 6272–6276 (1986).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  14. Vale, R. D. & Milligan, R. A. The way things move: looking under the hood of molecular motor proteins. Science 288, 88–95 (2000).

  15. Goldstein, L. S. & Philp, A. V. The road less traveled: emerging principles of kinesin motor utilization. Annu. Rev. Cell. Dev. Biol. 15, 141–83 (1999).

    Article  CAS  Google Scholar 

  16. Toyoshima, Y. Y. et al. Myosin subfragment-1 is sufficient to move actin filaments in vitro. Nature 328, 536–539 (1987).

    Article  CAS  Google Scholar 

  17. Kabsch, W. et al. Atomic structure of the actin:DNase I complex. Nature 347, 37–44 (1990).

    Article  CAS  Google Scholar 

  18. Rayment, I. et al. Three-dimensional structure of myosin subfragment-1: a molecular motor. Science 261, 50–58 (1993).

    Article  CAS  Google Scholar 

  19. Dominguez, R. et al. Crystal structure of a vertebrate smooth muscle myosin motor domain and its complex with the essential light chain: visualization of the pre-power stroke state. Cell 94, 559–571 (1998).

    Article  CAS  Google Scholar 

  20. Houdusse, A., Szent-Gyorgyi, A. G. & Cohen, C. Three conformational states of scallop myosin S1. Proc. Natl Acad. Sci. USA 97, 11238–11243 (2000).

    Article  CAS  Google Scholar 

  21. Smith, C. A. & Rayment, I. X-ray structure of the magnesium (II) ADP. vanadate complex of the Dictyostelium discoideum myosin motor domain to 1.9 Å resolution. Biochemistry 35, 5404–5417 (1996).

    Article  CAS  Google Scholar 

  22. Rayment, I. et al. Structure of the actin-myosin complex and its implications for muscle contraction. Science 261, 58–65 (1993).

    Article  CAS  Google Scholar 

  23. Schröder, R. R. et al. Three-dimensional atomic model of F-actin decorated with Dictyostelium myosin S1. Nature 364, 171–174 (1993).

    Article  Google Scholar 

  24. Jontes, J. D., Wilson-Kubalek, E. M. & Milligan, R. A. A 32 degree tail swing in brush border myosin I on ADP release. Nature 378, 751–753 (1995).

    Article  CAS  Google Scholar 

  25. Whittaker, M. et al. A 35-Å movement of smooth muscle myosin on ADP release. Nature 387, 748–751 (1995).

    Article  Google Scholar 

  26. Cooke, R., Crowder, M. S. & Thomas, D. D. Orientation of spin labels attached to cross-bridges in contracting muscle fibres. Nature 300, 776–778 (1982).

    Article  CAS  Google Scholar 

  27. Cooke, R. The mechanism of muscle contraction. CRC Crit. Rev. Biochem. 21, 53–118 (1986).

    Article  CAS  Google Scholar 

  28. Shih, W. M. et al. A FRET-based sensor reveals large ATP hydrolysis-induced conformational changes and three distinct states of the molecular motor myosin. Cell 102, 683–694 (2000).

    Article  CAS  Google Scholar 

  29. Yanagida, T., Arata, T. & Oosawa, F. Sliding distance of actin filament induced by a myosin crossbridge during one ATP hydrolysis cycle. Nature 316, 366–369 (1985).

    Article  CAS  Google Scholar 

  30. Harada, Y. et al. Mechanochemical coupling in actomyosin energy transduction studied by in vitro movement assay. J. Mol. Biol. 216, 49–68 (1990).

    Article  CAS  Google Scholar 

  31. Finer, J. T., Simmons, R. M. & Spudich, J. A. Single myosin molecule mechanics: piconewton forces and nanometre steps. Nature 368, 113–119 (1994).

    Article  CAS  Google Scholar 

  32. Yanagida, T. & Iwane, A. H. A large step for myosin. Proc. Natl Acad. Sci. USA 97, 9357–9359 (2000).

    Article  CAS  Google Scholar 

  33. Ruppel, K. M. & Spudich, J. A. Structure–function analysis of the motor domain of myosin. Annu. Rev. Cell Dev. Biol. 12, 543–73 (1996).

    Article  CAS  Google Scholar 

  34. Mercer, J. A. et al. Novel myosin heavy chain encoded by murine dilute coat colour locus. Nature 349, 709–713 (1991).

    Article  CAS  Google Scholar 

  35. 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 

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

    Article  CAS  Google Scholar 

  37. 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 

  38. Sakamoto, T. et al. Direct observation of processive movement by individual myosin V molecules. Biochem. Biophys. Res. Commun. 272, 586–590 (2000).

    Article  CAS  Google Scholar 

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

    Article  CAS  Google Scholar 

  40. De La Cruz, E. M. et al. The kinetic mechanism of myosin V. Proc. Natl Acad. Sci. USA 96, 13726–13731 (1999).

    Article  CAS  Google Scholar 

  41. De La Cruz, E. M., Sweeney, H. L. & Ostap, E. M. ADP inhibition of Myosin V ATPase Activity. Biophys. J. 79, 1524–1429 (2000).

    Article  CAS  Google Scholar 

  42. Trybus, K. M., Krementsova, E. & Freyzon, Y. Kinetic characterization of a monomeric unconventional myosin V construct. J. Biol. Chem. 274, 27448–27456 (1999).

    Article  CAS  Google Scholar 

  43. 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 

  44. Holmes, K. C. et al. Atomic model of the actin filament. Nature 347, 44–49 (1990).

    Article  CAS  Google Scholar 

  45. Lorenz, M., Popp, D. & Holmes, K. C. Refinement of the F-actin model against X-ray fiber diffraction data by the use of a directed mutation algorithm. J. Mol. Biol. 234, 826–836 (1993).

    Article  CAS  Google Scholar 

  46. Funatsu, T. et al. Imaging of single fluorescent molecules and individual ATP turnovers by single myosin molecules in aqueous solution. Nature 374, 555–559 (1995).

    Article  CAS  Google Scholar 

  47. Visscher, K., Schnitzer, M. J. & Block, S. M. Single kinesin molecules studied with a molecular force clamp. Nature 400, 184–189 (1999).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Biochemistry and Department of Developmental Biology, Beckman Center, B400, Stanford University School of Medicine, Stanford, 94305-5307, California, USA

    James A. Spudich

Authors
  1. James A. Spudich
    View author publications

    You can also search for this author in PubMed Google Scholar

Related links

Related links

DATABASE LINKS

myosin

kinesin family

myosin II

myosin V

ENCYCLOPEDIA OF LIFE SCIENCES

Motor proteins

Actin and actin filaments

Rights and permissions

Reprints and permissions

About this article

Cite this article

Spudich, J. The myosin swinging cross-bridge model. Nat Rev Mol Cell Biol 2, 387–392 (2001). https://doi.org/10.1038/35073086

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/35073086

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing