• A Corrigendum to this article was published on 30 June 2015

This article has been updated

Abstract

X-ray free-electron laser (XFEL) sources enable the use of crystallography to solve three-dimensional macromolecular structures under native conditions and without radiation damage. Results to date, however, have been limited by the challenge of deriving accurate Bragg intensities from a heterogeneous population of microcrystals, while at the same time modeling the X-ray spectrum and detector geometry. Here we present a computational approach designed to extract meaningful high-resolution signals from fewer diffraction measurements.

Access optionsAccess options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

Change history

  • 03 June 2015

    In the version of this article initially published, the authors claimed that with the tool cctbx.xfel, weak diffraction signals can be measured using fewer crystal specimens than are needed for the previously available program CrystFEL. However, there is not enough evidence to support this claim. The inaccurate statements have been corrected in the HTML and PDF versions of the article.

Accessions

Primary accessions

Protein Data Bank

Referenced accessions

References

  1. 1.

    et al. Nature 406, 752–757 (2000).

  2. 2.

    et al. Proc. Natl. Acad. Sci. USA 109, 19103–19107 (2012).

  3. 3.

    et al. Science 340, 491–495 (2013).

  4. 4.

    et al. Nature 470, 73–77 (2011).

  5. 5.

    et al. Nat. Methods 9, 259–262 (2012).

  6. 6.

    et al. Science 339, 227–230 (2013).

  7. 7.

    & Acta Crystallogr. D Biol. Crystallogr. 62, 58–64 (2006).

  8. 8.

    et al. Acta Crystallogr. D Biol. Crystallogr. 69, 1274–1282 (2013).

  9. 9.

    et al. J. Appl. Cryst. 45, 335–341 (2012).

  10. 10.

    et al. Science 337, 362–364 (2012).

  11. 11.

    , & J. Appl. Cryst. 37, 399–409 (2004).

  12. 12.

    & J. Appl. Cryst. 43, 611–616 (2010).

  13. 13.

    , & Acta Crystallogr. D Biol. Crystallogr. 69, 1195–1203 (2013).

  14. 14.

    et al. Acta Crystallogr. A 67, 131–140 (2011).

  15. 15.

    & Science 336, 1030–1033 (2012).

  16. 16.

    et al. Opt. Express 18, 5713–5723 (2010).

  17. 17.

    et al. Nat. Methods 9, 263–265 (2012).

  18. 18.

    , & Acta Crystallogr. A 35, 901–911 (1979).

  19. 19.

    et al. J. Appl. Cryst. 12, 570–581 (1979).

  20. 20.

    et al. Appl. Phys. Lett. 101, 034103 (2012).

  21. 21.

    J. Biochem. 112, 335–340 (1992).

  22. 22.

    et al. Nature 238, 35–37 (1972).

  23. 23.

    & New J. Phys. 12, 035024 (2010).

  24. 24.

    et al. Acta Crystallogr. D Biol. Crystallogr. 68, 1584–1587 (2012).

  25. 25.

    Anal. Chem. 85, 3464–3471 (2013).

  26. 26.

    et al. Proc. SPIE 8504, 85040C (2012).

  27. 27.

    Nat. Methods 9, 854–855 (2012).

  28. 28.

    et al. J. Appl. Cryst. 39, 112–119 (2006).

  29. 29.

    , & J. Appl. Cryst. 30, 1036–1040 (1997).

  30. 30.

    & Acta Crystallogr. D Biol. Crystallogr. 55, 1631–1640 (1999).

  31. 31.

    , & J. Appl. Cryst. 39, 158–168 (2006).

  32. 32.

    et al. Proc. Natl. Acad. Sci. USA 109, 9721–9726 (2012).

  33. 33.

    et al. Acta Crystallogr. D Biol. Crystallogr. 68, 649–658 (2012).

  34. 34.

    & Acta Crystallogr. D Biol. Crystallogr. 69, 1215–1222 (2013).

  35. 35.

    et al. Acta Crystallogr. D Biol. Crystallogr. 67, 608–618 (2011).

  36. 36.

    et al. Acta Crystallogr. D Biol. Crystallogr. 69, 1231–1240 (2013).

  37. 37.

    Acta Crystallogr. D Biol. Crystallogr. 54, 848–853 (1998).

  38. 38.

    & Methods Enzymol. 276, 307–326 (1997).

  39. 39.

    et al. Nat. Photonics 4, 641–647 (2010).

  40. 40.

    & J. Appl. Cryst. 15, 338–351 (1982).

  41. 41.

    & J. Appl. Cryst. 15, 493–508 (1982).

  42. 42.

    , & J. Appl. Cryst. 16, 242–250 (1983).

  43. 43.

    & J. Appl. Cryst. 28, 461–481 (1995).

  44. 44.

    Acta Crystallogr. D Biol. Crystallogr. 55, 1703–1717 (1999).

  45. 45.

    Acta Crystallogr. D Biol. Crystallogr. 65, 535–542 (2009).

  46. 46.

    , & J. Appl. Cryst. 43, 70–82 (2009).

  47. 47.

    et al. Acta Crystallogr. D Biol. Crystallogr. 67, 628–638 (2011).

  48. 48.

    & J. Appl. Cryst. 30, 65–70 (1997).

  49. 49.

    Acta Crystallogr. D Biol. Crystallogr. 62, 48–57 (2006).

  50. 50.

    et al. J. Appl. Cryst. 15, 330–337 (1982).

  51. 51.

    Nature 355, 472–475 (1992).

  52. 52.

    et al. Nucl. Instrum. Methods Phys. Res. A 614, 483–496 (2010).

  53. 53.

    et al. J. Appl. Cryst. 26, 180–184 (1993).

  54. 54.

    et al. J. Appl. Cryst. 40, 658–674 (2007).

  55. 55.

    et al. Acta Crystallogr. D Biol. Crystallogr. 66, 213–221 (2010).

  56. 56.

    et al. Proteins 37, 628–640 (1999).

  57. 57.

    et al. Acta Crystallogr. D Biol. Crystallogr. 64, 61–69 (2008).

  58. 58.

    et al. Acta Crystallogr. D Biol. Crystallogr. 68, 352–367 (2012).

  59. 59.

    et al. Acta Crystallogr. D Biol. Crystallogr. 66, 12–21 (2010).

  60. 60.

    et al. Acta Crystallogr. D Biol. Crystallogr. 65, 297–300 (2009).

  61. 61.

    et al. J. Appl. Cryst. 43, 669–676 (2010).

Download references

Acknowledgements

This work was supported by US National Institutes of Health (NIH) grants GM095887 and GM102520 and Director, Office of Science, US Department of Energy (DOE) under contract DE-AC02-05CH11231 for data-processing methods (N.K.S.); Director, DOE Office of Science, Office of Basic Energy Sciences (OBES), Chemical Sciences, Geosciences and Biosciences Division (CSGB) under contract DE-AC02-05CH11231 (J.Y. and V.K.Y.); NIH grant GM055302 (V.K.Y.); and NIH grant P41GM103393 (U.B.). Sample injection was supported by LCLS (M.J.B. and D.W.S.) and the Atomic, Molecular and Optical Science program, CSGB Division, OBES, DOE (M.J.B.), and through the SLAC National Accelerator Laboratory Directed Research and Development program (M.J.B. and H.L.). J.M. was supported by the Artificial Leaf Project Umeå (K&A Wallenberg Foundation), the Solar Fuels Strong Research Environment Umeå (Umeå University), Vetenskapsrådet and Swedish Energy Agency (Energimyndigheten). Experiments were carried out at the LCLS at SLAC, an Office of Science User Facility operated for the DOE by Stanford University. We thank A. Perazzo, M. Dubrovin, I. Ofte, and A. Salnikov for collaboration on data analysis, and C. Kenney for expertise related to the CSPAD detector.

Author information

Author notes

    • Richard J Gildea

    Present address: Diamond Light Source, Harwell Science and Innovation Campus, Didcot, Oxfordshire, UK.

Affiliations

  1. Physical Biosciences Division, Lawrence Berkeley National Laboratory, Berkeley, California, USA.

    • Johan Hattne
    • , Nathaniel Echols
    • , Rosalie Tran
    • , Jan Kern
    • , Richard J Gildea
    • , Aaron S Brewster
    • , Benedikt Lassalle-Kaiser
    • , Alyssa Lampe
    • , Guangye Han
    • , Sheraz Gul
    • , Petrus H Zwart
    • , Ralf W Grosse-Kunstleve
    • , Junko Yano
    • , Vittal K Yachandra
    • , Paul D Adams
    •  & Nicholas K Sauter
  2. Linac Coherent Light Source (LCLS), SLAC National Accelerator Laboratory, Menlo Park, California, USA.

    • Roberto Alonso-Mori
    • , Despina Milathianaki
    • , Alan R Fry
    • , Alan Miahnahri
    • , William E White
    • , Donald W Schafer
    • , M Marvin Seibert
    • , Jason E Koglin
    • , Michael J Bogan
    • , Marc Messerschmidt
    • , Garth J Williams
    • , Sébastien Boutet
    •  & Uwe Bergmann
  3. Max-Volmer-Laboratorium für Biophysikalische Chemie, Technische Universität, Berlin, Germany.

    • Carina Glöckner
    • , Julia Hellmich
    • , Dörte DiFiore
    •  & Athina Zouni
  4. Stanford PULSE Institute, SLAC National Accelerator Laboratory, Menlo Park, California, USA.

    • Hartawan Laksmono
    • , Raymond G Sierra
    •  & Michael J Bogan
  5. Stanford Synchrotron Radiation Lightsource, SLAC National Accelerator Laboratory, Menlo Park, California, USA.

    • Dimosthenis Sokaras
    • , Tsu-Chien Weng
    • , Jonas Sellberg
    •  & Matthew J Latimer
  6. Department of Physics, AlbaNova, Stockholm University, Stockholm, Sweden.

    • Jonas Sellberg
  7. European Synchrotron Radiation Facility, Grenoble, France.

    • Pieter Glatzel
  8. Institutionen för Kemi, Kemiskt Biologiskt Centrum, Umeå Universitet, Umeå, Sweden.

    • Johannes Messinger
  9. Institut für Biologie, Humboldt Universität zu Berlin, Berlin, Germany.

    • Athina Zouni

Authors

  1. Search for Johan Hattne in:

  2. Search for Nathaniel Echols in:

  3. Search for Rosalie Tran in:

  4. Search for Jan Kern in:

  5. Search for Richard J Gildea in:

  6. Search for Aaron S Brewster in:

  7. Search for Roberto Alonso-Mori in:

  8. Search for Carina Glöckner in:

  9. Search for Julia Hellmich in:

  10. Search for Hartawan Laksmono in:

  11. Search for Raymond G Sierra in:

  12. Search for Benedikt Lassalle-Kaiser in:

  13. Search for Alyssa Lampe in:

  14. Search for Guangye Han in:

  15. Search for Sheraz Gul in:

  16. Search for Dörte DiFiore in:

  17. Search for Despina Milathianaki in:

  18. Search for Alan R Fry in:

  19. Search for Alan Miahnahri in:

  20. Search for William E White in:

  21. Search for Donald W Schafer in:

  22. Search for M Marvin Seibert in:

  23. Search for Jason E Koglin in:

  24. Search for Dimosthenis Sokaras in:

  25. Search for Tsu-Chien Weng in:

  26. Search for Jonas Sellberg in:

  27. Search for Matthew J Latimer in:

  28. Search for Pieter Glatzel in:

  29. Search for Petrus H Zwart in:

  30. Search for Ralf W Grosse-Kunstleve in:

  31. Search for Michael J Bogan in:

  32. Search for Marc Messerschmidt in:

  33. Search for Garth J Williams in:

  34. Search for Sébastien Boutet in:

  35. Search for Johannes Messinger in:

  36. Search for Athina Zouni in:

  37. Search for Junko Yano in:

  38. Search for Uwe Bergmann in:

  39. Search for Vittal K Yachandra in:

  40. Search for Paul D Adams in:

  41. Search for Nicholas K Sauter in:

Contributions

J. Hattne, J.K., J.Y., U.B., V.K.Y., P.D.A. and N.K.S. conceived of the new data-processing methods and analyzed the data; J. Hattne, N.E., R.J.G., A.S.B., R.W.G.-K., P.H.Z., M.M., P.D.A. and N.K.S. wrote the data-processing software; U.B., J.Y., V.K.Y., J.K., R.A.-M., J.M., A.Z., N.K.S., G.J.W., S.B., A.R.F., A.M., D.M., D.W.S., W.E.W. and M.J.B. designed the experiment; R.T., C.G., J. Hellmich, D.D., A.L., G.H., J.K. and A.Z. prepared samples; S.B., J.E.K., M.M., M.M.S., G.J.W. operated the CXI instrument; M.J.B., H.L., R.G.S., J.K., J.M., B.L.-K., S.G., R.T., C.G., J. Hellmich, J.S., D.W.S., A.M. and G.J.W. developed, tested and ran the sample delivery system; R.A.-M., U.B., M.J.B., S.B., N.E., R.J.G., P.G., C.G.,S.G., G.H., J.Hattne., J.Hellmich, J.K., J.E.K., H.L., A.L., B.L.-K., D.M., M.M., J.M., N.K.S., M.M.S., J.S., R.G.S., D.S., R.T., T.-C.W., G.J.W., V.K.Y., J.Y. and A.Z. performed the LCLS experiment; J. Hattne, N.E., J.K., J.Y., U.B., V.K.Y., P.D.A. and N.K.S. wrote the manuscript with input from all authors.

Competing interests

The authors declare no competing financial interests.

Corresponding author

Correspondence to Nicholas K Sauter.

Supplementary information

PDF files

  1. 1.

    Supplementary Text and Figures

    Supplementary Figures 1 and 2, Supplementary Tables 1–3, and Supplementary Note

About this article

Publication history

Received

Accepted

Published

DOI

https://doi.org/10.1038/nmeth.2887

Further reading