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How good can cryo-EM become?

Nature Methods volume 13, pages 28–32 (2016)Cite this article

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Abstract

The suddenness with which single-particle cryo-electron microscopy (cryo-EM) has emerged as a method for determining high-resolution structures of biological macromolecules invites the questions, how much better can this technology get, and how fast is that likely to happen? Though we can rightly celebrate the maturation of cryo-EM as a high-resolution structure-determination tool, I believe there still are many developments to look forward to.

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Figure 1: Comparison of cryo-EM images of recombinant Thermoplasma acidophilum 20S proteasomes.

References

  1. Nogales, E. Nat. Methods 13, 24–27 (2016).

    Article  CAS  Google Scholar 

  2. Henderson, R. Q. Rev. Biophys. 28, 171–193 (1995).

    Article  CAS  Google Scholar 

  3. Glaeser, R.M. J. Struct. Biol. 128, 3–14 (1999).

    Article  CAS  Google Scholar 

  4. Rosenthal, P.B. & Henderson, R. J. Mol. Biol. 333, 721–745 (2003).

    Article  CAS  Google Scholar 

  5. Taylor, K.A. & Glaeser, R.M. J. Struct. Biol. 163, 214–223 (2008).

    Article  CAS  Google Scholar 

  6. Kastner, B. et al. Nat. Methods 5, 53–55 (2008).

    Article  CAS  Google Scholar 

  7. Chari, A. et al. Nat. Methods 12, 859–865 (2015).

    Article  CAS  Google Scholar 

  8. Kelly, D.F., Dukovski, D. & Walz, T. Methods Enzymol. 481, 83–107 (2010).

    Article  CAS  Google Scholar 

  9. Yu, G. et al. J. Struct. Biol. 187, 1–9 (2014).

    Article  CAS  Google Scholar 

  10. Crucifix, C., Uhring, M. & Schultz, P. J. Struct. Biol. 146, 441–451 (2004).

    Article  CAS  Google Scholar 

  11. Dashti, A. et al. Proc. Natl. Acad. Sci. USA 111, 17492–17497 (2014).

    Article  CAS  Google Scholar 

  12. Scheres, S.H.W. J. Struct. Biol. 180, 519–530 (2012).

    Article  CAS  Google Scholar 

  13. Callaway, E. Nature 525, 172–174 (2015).

    Article  CAS  Google Scholar 

  14. Zernike, F. Science 121, 345–349 (1955).

    Article  CAS  Google Scholar 

  15. Boersch, H. Z. Naturforschung A J. Phys. Sci. 2, 615–633 (1947).

    Google Scholar 

  16. Danev, R., Buijsse, B., Khoshouei, M., Plitzko, J.M. & Baumeister, W. Proc. Natl. Acad. Sci. USA 111, 15635–15640 (2014).

    Article  CAS  Google Scholar 

  17. Scheres, S.H. eLife 3, e03665 (2014).

    Article  Google Scholar 

  18. Bartesaghi, A., Matthies, D., Banerjee, S., Merk, A. & Subramaniam, S. Proc. Natl. Acad. Sci. USA 111, 11709–11714 (2014).

    Article  CAS  Google Scholar 

  19. Breedlove, J.R. & Trammell, G.T. Science 170, 1310–1313 (1970).

    Article  CAS  Google Scholar 

  20. Frank, J. Three-dimensional Electron Microscopy of Macromolecular Assemblies—Visualization of Biological Molecules in Their Native State (Oxford University Press, New York, 2006).

    Book  Google Scholar 

  21. Glaeser, R.M., Downing, K., DeRosier, D., Chiu, W. & Frank, J. Electron Crystallography of Biological Macromolecules (Oxford University Press, New York, 2007).

    Google Scholar 

  22. Jensen, G.J. Cryo-EM (Academic Press, 2010).

    Google Scholar 

  23. Schmidt-Krey, I. & Cheng, Y. Electron Crystallography of Soluble and Membrane Proteins: Methods and Protocols (Springer, New York, 2013).

    Book  Google Scholar 

  24. Glaeser, R.M. J. Ultrastruct. Res. 36, 466–482 (1971).

    Article  CAS  Google Scholar 

  25. DeRosier, D.J. Ultramicroscopy 81, 83–98 (2000).

    Article  CAS  Google Scholar 

  26. Leong, P.A., Yu, X., Zhou, Z.H. & Jensen, G.J. Methods Enzymol. 482, 369–380 (2010).

    Article  Google Scholar 

  27. Wolf, M., DeRosier, D.J. & Grigorieff, N. Ultramicroscopy 106, 376–382 (2006).

    Article  CAS  Google Scholar 

  28. Agard, D., Cheng, Y.F., Glaeser, R.M. & Subramaniam, S. in Advances in Imaging and Electron Physics vol. 185 (ed. Hawkes, P.W.) 113–137 (Academic Press, 2014).

    Google Scholar 

  29. Cohen, H.A., Schmid, M.F. & Chiu, W. Ultramicroscopy 14, 219–226 (1984).

    Article  CAS  Google Scholar 

  30. Kaiser, D. How the Hippies Saved Physics: Science, Counterculture, and the Quantum Revival (W.W. Norton, New York, 2011).

    Google Scholar 

  31. Kwiat, P., Weinfurter, H., Herzog, T., Zeilinger, A. & Kasevich, M.A. Phys. Rev. Lett. 74, 4763–4766 (1995).

    Article  CAS  Google Scholar 

  32. Putnam, W.P. & Yanik, M.F. Phys. Rev. A 80, 040902(R) (2009).

    Article  Google Scholar 

  33. Kruit, P. et al. Preprint at http://arxiv.org/ftp/arxiv/papers/1510/1510.05946.pdf (20 October 2015).

  34. Mitchison, G. & Massar, S. Phys. Rev. A 63, 032105 (2001).

    Article  Google Scholar 

  35. Okamoto, H. Phys. Rev. A 85, 043810 (2012).

    Article  Google Scholar 

  36. Okamoto, H. & Nagatani, Y. Appl. Phys. Lett. 104, 062604 (2014).

    Article  Google Scholar 

  37. Volkmann, H. Appl. Optics 5, 1720–1731 (1966).

    Article  CAS  Google Scholar 

  38. Henderson, R. Proc. Natl. Acad. Sci. USA 110, 18037–18041 (2013).

    Article  CAS  Google Scholar 

  39. Chen, S. et al. Ultramicroscopy 135, 24–35 (2013).

    Article  CAS  Google Scholar 

  40. Wu, S. et al. Structure 20, 582–592 (2012).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The writing of this commentary has been supported in part by US National Institutes of Health grant GM083039. I want to especially thank R. Danev for providing the pair of images used to prepare Figure 1.

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  1. Robert M. Glaeser is at the Lawrence Berkeley National Laboratory, University of California, Berkeley, California, USA.,

    Robert M Glaeser

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  1. Robert M Glaeser
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Correspondence to Robert M Glaeser.

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The author declares no competing financial interests.

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Glaeser, R. How good can cryo-EM become?. Nat Methods 13, 28–32 (2016). https://doi.org/10.1038/nmeth.3695

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