Identification of cross-linked peptides from large sequence databases (original) (raw)

Nature Methods volume 5, pages 315–318 (2008)Cite this article

A Corrigendum to this article was published on 01 August 2008

This article has been updated

Abstract

NOTE: In the version of this Brief Communication initially published, an author name (Lukas Mueller) was incorrect. The correct author name is Lukas N Mueller. The error has been corrected in the HTML and PDF versions of the article.

We describe a method to identify cross-linked peptides from complex samples and large protein sequence databases by combining isotopically tagged cross-linkers, chromatographic enrichment, targeted proteomics and a new search engine called xQuest. This software reduces the search space by an upstream candidate-peptide search before the recombination step. We showed that xQuest can identify cross-linked peptides from a total Escherichia coli lysate with an unrestricted database search.

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

Access options

Subscribe to this journal

Receive 12 print issues and online access

$259.00 per year

only $21.58 per issue

Buy this article

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

Additional access options:

Similar content being viewed by others

Change history

In the version of this Brief Communication initially published, an author name (Lukas Mueller) was incorrect. The correct author name is Lukas N Mueller. The error has been corrected in the HTML and PDF versions of the article.

References

  1. Young, M.M. et al. Proc. Natl. Acad. Sci. USA 97, 5802–5806 (2000).
    Article CAS Google Scholar
  2. Sinz, A. J. Mass Spectrom. 38, 1225–1237 (2003).
    Article CAS Google Scholar
  3. Seebacher, J. et al. J. Proteome Res. 5, 2270–2282 (2006).
    Article CAS Google Scholar
  4. Ihling, C. et al. J. Am. Soc. Mass Spectrom. 17, 1100–1113 (2006).
    Article CAS Google Scholar
  5. Muller, D.R. et al. Anal. Chem. 73, 1927–1934 (2001).
    Article CAS Google Scholar
  6. Dihazi, G.H. & Sinz, A. Rapid Commun. Mass Spectrom. 17, 2005–2014 (2003).
    Article CAS Google Scholar
  7. Huang, B.X., Kim, H.Y. & Dass, C. J. Am. Soc. Mass Spectrom. 15, 1237–1247 (2004).
    Article CAS Google Scholar
  8. Novak, P. et al. Anal. Chem. 77, 5101–5106 (2005).
    Article CAS Google Scholar
  9. Pearson, K.M., Pannell, L.K. & Fales, H.M. Rapid Commun. Mass Spectrom. 16, 149–159 (2002).
    Article CAS Google Scholar
  10. Gao, Q. et al. Anal. Chem. 78, 2145–2149 (2006).
    Article CAS Google Scholar
  11. Schilling, B., Row, R.H., Gibson, B.W., Guo, X. & Young, M.M. J. Am. Soc. Mass Spectrom. 14, 834–850 (2003).
    Article CAS Google Scholar
  12. de Koning, L.J. et al. FEBS J. 273, 281–291 (2006).
    Article CAS Google Scholar
  13. Back, J.W., de Jong, L., Muijsers, A.O. & de Koster, C.G. J. Mol. Biol. 331, 303–313 (2003).
    Article CAS Google Scholar
  14. Sinz, A., Kalkhof, S. & Ihling, C. J. Am. Soc. Mass Spectrom. 16, 1921–1931 (2005).
    Article CAS Google Scholar
  15. Trester-Zedlitz, M. et al. J. Am. Chem. Soc. 125, 2416–2425 (2003).
    Article CAS Google Scholar

Download references

Acknowledgements

O.R. was supported by fellowships of the Deutsche Forschungsgemeinschaft and the Roche Research Foundation; M.B. was supported by a long-term fellowship of the European Molecular Biology Organization and a Marie Curie fellowship of the European Commission. A.S. was supported in part by a grant from F. Hoffmann–La Roche Ltd provided to the Competence Center for Systems Physiology and Metabolic Disease. The work was supported in part with Federal funds from the US National Heart, Lung and Blood Institute, National Institutes of Health (contract N01-HV-28179) and with funds from ETH Zurich.

Author information

Authors and Affiliations

  1. Institute of Molecular Systems Biology, Eidgenössische Technische Hochschule (ETH) Zurich, Wolfgang-Pauli Strasse 16, Zurich, 8093, Switzerland
    Oliver Rinner, Thomas Walzthoeni, Lukas N Mueller, Martin Beck, Alexander Schmidt, Markus Mueller & Ruedi Aebersold
  2. Institute for Systems Biology, 1441 North 34th Street, Seattle, 98103, Washington, USA
    Jan Seebacher & Ruedi Aebersold
  3. University of Innsbruck, Innrain 52, Innsbruck, A-6020, Austria
    Thomas Walzthoeni
  4. Faculty of Science, University of Zurich, Winterthurerstrasse 190, Zurich, 8057, Switzerland
    Alexander Schmidt & Ruedi Aebersold

Authors

  1. Oliver Rinner
    You can also search for this author inPubMed Google Scholar
  2. Jan Seebacher
    You can also search for this author inPubMed Google Scholar
  3. Thomas Walzthoeni
    You can also search for this author inPubMed Google Scholar
  4. Lukas N Mueller
    You can also search for this author inPubMed Google Scholar
  5. Martin Beck
    You can also search for this author inPubMed Google Scholar
  6. Alexander Schmidt
    You can also search for this author inPubMed Google Scholar
  7. Markus Mueller
    You can also search for this author inPubMed Google Scholar
  8. Ruedi Aebersold
    You can also search for this author inPubMed Google Scholar

Contributions

O.R. was responsible for most of the software design and programming, conducted most of the experiments and most of the data evaluation; J.S. synthesized the cross-linker and contributed to software design; T.W. contributed to scoring, data evaluation and part of experiments; L.N.M. analyzed and aligned MS1 data; M.B. performed part of experiments and evaluated data; A.S. designed mass spectrometric methods for analyzing cross-linked samples; M.M. contributed to scoring; R.A. coordinated the project, contributed ideas and concept.

Corresponding author

Correspondence toRuedi Aebersold.

Supplementary information

Supplementary Text and Figures

Supplementary Figures 1–5, Supplementary Tables 1–2, Supplementary Results, Supplementary Discussion, Supplementary Methods (PDF 1982 kb)

Rights and permissions

About this article

Cite this article

Rinner, O., Seebacher, J., Walzthoeni, T. et al. Identification of cross-linked peptides from large sequence databases.Nat Methods 5, 315–318 (2008). https://doi.org/10.1038/nmeth.1192

Download citation