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Cutting the forest to see a single tree?

Nature Chemical Biology volume 4, pages 440–443 (2008)Cite this article

The development of single-molecule tools has significantly impacted the way we think about biochemical processes. Watching a single protein in action allows us to observe kinetic details and rare subpopulations that are hidden in ensemble-averaging techniques. I will discuss here the pros and cons of the single-molecule approach in studying ligand binding in macromolecular systems and how these techniques can be applied to characterize the behavior of large multicomponent biochemical systems.

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Figure 1: Fluctuating turnover rates and binding affinities of enzymes.
Figure 2: Fractional binding in single-molecule and bulk-phase experiments.

References

  1. Rissin, D.M., Gorris, H.H. & Walt, D.R. J. Am. Chem. Soc. 130, 5349–5353 (2008).

    Article  CAS  Google Scholar 

  2. Flomenbom, O. et al. Proc. Natl. Acad. Sci. USA 102, 2368–2372 (2005).

    Article  CAS  Google Scholar 

  3. English, B.P. et al. Nat. Chem. Biol. 2, 87–94 (2006).

    Article  CAS  Google Scholar 

  4. van Oijen, A.M. et al. Science 301, 1235–1239 (2003).

    Article  CAS  Google Scholar 

  5. Abbondanzieri, E.A., Greenleaf, W.J., Shaevitz, J.W., Landick, R. & Block, S.M. Nature 438, 460–465 (2005).

    Article  CAS  Google Scholar 

  6. Dumont, S. et al. Nature 439, 105–108 (2006).

    Article  CAS  Google Scholar 

  7. Myong, S., Rasnik, I., Joo, C., Lohman, T.M. & Ha, T. Nature 437, 1321–1325 (2005).

    Article  CAS  Google Scholar 

  8. Yildiz, A. et al. Science 300, 2061–2065 (2003).

    Article  CAS  Google Scholar 

  9. Yildiz, A., Tomishige, M., Vale, R.D. & Selvin, P.R. Science 303, 676–678 (2004).

    Article  CAS  Google Scholar 

  10. Edman, L. & Rigler, R. Proc. Natl. Acad. Sci. USA 97, 8266–8271 (2000).

    Article  CAS  Google Scholar 

  11. Lu, H.P., Xun, L. & Xie, X.S. Science 282, 1877–1882 (1998).

    Article  CAS  Google Scholar 

  12. Yang, H. et al. Science 302, 262–266 (2003).

    Article  CAS  Google Scholar 

  13. Cornish-Bowden, A. & Cardenas, M.L. J. Theor. Biol. 124, 1–23 (1987).

    Article  CAS  Google Scholar 

  14. Qian, H. Biophys J. published online, doi:10.1529/biophysj.108.131771 (25 April 2008).

  15. Cornish, P.V. & Ha, T. ACS Chem. Biol. 2, 53–61 (2007).

    Article  CAS  Google Scholar 

  16. Rimsky, S. Curr. Opin. Microbiol. 7, 109–114 (2004).

    Article  CAS  Google Scholar 

  17. Amit, R., Oppenheim, A.B. & Stavans, J. Biophys. J. 84, 2467–2473 (2003).

    Article  CAS  Google Scholar 

  18. Tupper, A.E. et al. EMBO J. 13, 258–268 (1994).

    Article  CAS  Google Scholar 

  19. Amit, R., Oppenheim, A.B. & Stavans, J. Biophys. J. 87, 1392–1393 (2004).

    Article  CAS  Google Scholar 

  20. Dame, R.T. & Wuite, G.J. Biophys. J. 85, 4146–4148 (2003).

    Article  CAS  Google Scholar 

  21. Tanner, N.A. et al. Nat. Struct. Mol. Biol. 15, 170–176 (2008).

    Article  CAS  Google Scholar 

  22. Lee, J.-B. et al. Nature 439, 621–624 (2006).

    Article  CAS  Google Scholar 

  23. van Oijen, A.M. Biopolymers 85, 144–153 (2007).

    Article  CAS  Google Scholar 

  24. Ha, T. Methods 25, 78–86 (2001).

    Article  CAS  Google Scholar 

  25. Levene, M.J. et al. Science 299, 682–686 (2003).

    Article  CAS  Google Scholar 

  26. Klar, T.A., Jakobs, S., Dyba, M., Egner, A. & Hell, S.W. Proc. Natl. Acad. Sci. USA 97, 8206–8210 (2000).

    Article  CAS  Google Scholar 

  27. Benitez, J.J. et al. J. Am. Chem. Soc. 130, 2446–2447 (2008).

    Article  CAS  Google Scholar 

  28. Cisse, I., Okumus, B., Joo, C. & Ha, T. Proc. Natl. Acad. Sci. USA 104, 12646–12650 (2007).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The author acknowledges funding from the US National Institutes of Health, the US National Science Foundation and the Searle Scholars Program. The author thanks J. Loparo for a critical reading of the manuscript.

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  1. Department of Biological Chemistry and Molecular Pharmacology, Antoine M. van Oijen is at Harvard Medical School, 240 Longwood Avenue, SGM204A, Boston, Massachusetts 02115, USA. antoine_van_oijen@hms.harvard.edu,

    Antoine M van Oijen

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van Oijen, A. Cutting the forest to see a single tree?. Nat Chem Biol 4, 440–443 (2008). https://doi.org/10.1038/nchembio0808-440

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