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.

  • Commentary
  • Published:

Coordinating the impact of structural genomics on the human α-helical transmembrane proteome

Nature Structural & Molecular Biology volume 20, pages 135–138 (2013)Cite this article

Subjects

Given the recent successes in determining membrane-protein structures, we explore the tractability of determining representatives for the entire human membrane proteome. This proteome contains 2,925 unique integral α-helical transmembrane-domain sequences that cluster into 1,201 families sharing more than 25% sequence identity. Structures of 100 optimally selected targets would increase the fraction of modelable human α-helical transmembrane domains from 26% to 58%, providing structure and function information not otherwise available.

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: Flowchart of the analysis (Supplementary Notes 1 and 2).

References

  1. Punta, M. et al. Methods 41, 460–474 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Fagerberg, L., Jonasson, K., von Heijne, G., Uhlen, M. & Berglund, L. Proteomics 10, 1141–1149 (2010).

    Article  CAS  PubMed  Google Scholar 

  3. Punta, M. et al. J. Struct. Funct. Genomics 10, 255–268 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  4. UniProt Consortium. Nucleic Acids Res. 40, D71–D75 (2012).

  5. Hopkins, A.L. & Groom, C.R. Nat. Rev. Drug Discov. 1, 727–730 (2002).

    CAS  PubMed  Google Scholar 

  6. Giacomini, K.M. et al. Nat. Rev. Drug Discov. 9, 215–236 (2010).

    Article  CAS  PubMed  Google Scholar 

  7. Rose, P.W. et al. Nucleic Acids Res. 39, D392–D401 (2011).

    Article  CAS  PubMed  Google Scholar 

  8. Kloppmann, E., Punta, M. & Rost, B. Curr. Opin. Struct. Biol. 22, 326–332 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Hopf, T.A. et al. Cell 149, 1607–1621 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Baker, D. & Sali, A. Science 294, 93–96 (2001).

    Article  CAS  PubMed  Google Scholar 

  11. Dunbrack, R.L. Jr. Curr. Opin. Struct. Biol. 16, 374–384 (2006).

    Article  CAS  PubMed  Google Scholar 

  12. Liu, T., Tang, G.W. & Capriotti, E. Comb. Chem. High Throughput Screen. 14, 532–547 (2011).

    Article  PubMed  Google Scholar 

  13. Granseth, E., Seppala, S., Rapp, M., Daley, D.O. & Von Heijne, G. Mol. Membr. Biol. 24, 329–332 (2007).

    Article  CAS  PubMed  Google Scholar 

  14. Norvell, J.C. & Berg, J.M. Structure 15, 1519–1522 (2007).

    Article  CAS  PubMed  Google Scholar 

  15. Vitkup, D., Melamud, E., Moult, J. & Sander, C. Nat. Struct. Biol. 8, 559–566 (2001).

    Article  CAS  PubMed  Google Scholar 

  16. Marsden, R.L. & Orengo, C.A. Methods Mol. Biol. 426, 3–25 (2008).

    Article  CAS  PubMed  Google Scholar 

  17. Raftery, J. Methods Mol. Biol. 426, 37–47 (2008).

    Article  CAS  PubMed  Google Scholar 

  18. Büssow, K. et al. Microb. Cell Fact. 4, 21 (2005).

    Article  PubMed  PubMed Central  Google Scholar 

  19. Kelly, L. et al. J. Struct. Funct. Genomics 10, 269–280 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  20. Martí-Renom, M.A. et al. Annu. Rev. Biophys. Biomol. Struct. 29, 291–325 (2000).

    Article  PubMed  Google Scholar 

  21. Carlsson, J. et al. Nat. Chem. Biol. 7, 769–778 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Schlessinger, A. et al. Proc. Natl. Acad. Sci. USA 108, 15810–15815 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. UniProt Consortium. Nucleic Acids Res. 38, D142–D148 (2010).

  24. Vroling, B. et al. Nucleic Acids Res. 39, D309–D319 (2011).

    Article  CAS  PubMed  Google Scholar 

  25. Katritch, V., Cherezov, V. & Stevens, R.C. Trends Pharmacol. Sci. 33, 17–27 (2012).

    Article  CAS  PubMed  Google Scholar 

  26. Granier, S. et al. Nature 485, 400–404 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Schlessinger, A. et al. Protein Sci. 19, 412–428 (2010).

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Mineta, K. et al. FEBS Lett. 585, 606–612 (2011).

    Article  CAS  PubMed  Google Scholar 

  29. Escudero-Esparza, A., Jiang, W.G. & Martin, T.A. Front. Biosci. 16, 1069–1083 (2011).

    Article  CAS  Google Scholar 

  30. Angelow, S., Ahlstrom, R. & Yu, A.S. Am. J. Physiol. Renal Physiol. 295, F867–F876 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Krause, G. et al. Biochim. Biophys. Acta 1778, 631–645 (2008).

    Article  CAS  PubMed  Google Scholar 

  32. Larsson, T.P., Murray, C.G., Hill, T., Fredriksson, R. & Schioth, H.B. FEBS Lett. 579, 690–698 (2005).

    Article  CAS  PubMed  Google Scholar 

  33. Krogh, A., Larsson, B., von Heijne, G. & Sonnhammer, E.L. J. Mol. Biol. 305, 567–580 (2001).

    Article  CAS  PubMed  Google Scholar 

  34. Edgar, R.C. Bioinformatics 26, 2460–2461 (2010).

    Article  CAS  PubMed  Google Scholar 

  35. Pieper, U. et al. Nucleic Acids Res. 39, D465–D474 (2011).

    Article  CAS  PubMed  Google Scholar 

  36. Johnson, M. et al. Nucleic Acids Res. 36, W5–W9 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We thank I. Wilson, H. Berman, J. Chin and P. Preusch for critical comments on the manuscript. Research was supported by the US National Institutes of Health PSI:Biology grants U54 GM094662 (A.S., U.P.), U54 GM094618 (R.C.S.), U54 GM094625 (R.M.S., A.S., U.P.), U54 GM094584 (B.G.F.), U54 GM094599 (P.F.), U54 GM094611 (M.C.W., M.E.D., M.G.M.), U54 GM094610 (G.A.C., D.C.R., M.H.B.S.), U54 GM094608 (J.J.C.), U54 GM095315 (W.A.H., B.R., E.K.) and U54 GM094598 (D.L.S.).

Author information

Author notes

  1. Avner Schlessinger

    Present address: Present address: Department of Pharmacology and Systems Therapeutics, Mount Sinai School of Medicine, New York, New York, USA.,

Authors and Affiliations

  1. Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, San Francisco, California, USA

    Ursula Pieper, Avner Schlessinger & Andrej Sali

  2. Department of Pharmaceutical Chemistry, University of California, San Francisco, San Francisco, California, USA

    Ursula Pieper, Avner Schlessinger & Andrej Sali

  3. California Institute for Quantitative Biosciences, University of California, San Francisco, San Francisco, California, USA

    Ursula Pieper, Avner Schlessinger & Andrej Sali

  4. Department of Bioinformatics and Computational Biology, Technical University Munich, Fakultät für Informatik, Garching, Germany

    Edda Kloppmann & Burkhard Rost

  5. Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, California, USA

    Geoffrey A Chang & Raymond C Stevens

  6. Harvard University Medical School, Boston, Massachusetts, USA

    James J Chou

  7. School of Medicine and Dentistry, University of Rochester Medical Center, Rochester, New York, USA

    Mark E Dumont

  8. Transmembrane Protein Center, University of Wisconsin–Madison, Madison, Wisconsin, USA

    Brian G Fox

  9. Department of Chemistry and Biochemistry, Arizona State University, Tempe, Arizona, USA

    Petra Fromme

  10. New York Structural Biology Center, New York, New York, USA

    Wayne A Hendrickson & David L Stokes

  11. Hauptman Woodward Medical Research Institute, Buffalo, New York, USA

    Michael G Malkowski

  12. Division of Chemistry and Chemical Engineering, Howard Hughes Medical Institute, California Institute of Technology, Pasadena, California, USA

    Douglas C Rees

  13. Molecular, Cellular and Developmental Biology, University of Colorado Boulder, Boulder, Colorado, USA

    Michael H B Stowell

  14. Department of Molecular Physiology and Biological Physics, University of Virginia, Charlottesville, Virginia, USA

    Michael C Wiener

  15. Department of Biochemistry and Biophysics, University of California, San Francisco, San Francisco, California, USA

    Robert M Stroud

Authors
  1. Ursula Pieper
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Avner Schlessinger
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Edda Kloppmann
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Geoffrey A Chang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. James J Chou
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Mark E Dumont
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Brian G Fox
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Petra Fromme
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Wayne A Hendrickson
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Michael G Malkowski
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Douglas C Rees
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. David L Stokes
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Michael H B Stowell
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Michael C Wiener
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Burkhard Rost
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Robert M Stroud
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Raymond C Stevens
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Andrej Sali
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Robert M Stroud, Raymond C Stevens or Andrej Sali.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Figures, Tables and Notes

Supplementary Figures 1–4, Supplementary Tables 1–3 and Supplementary Notes 1–4 (PDF 1656 kb)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Pieper, U., Schlessinger, A., Kloppmann, E. et al. Coordinating the impact of structural genomics on the human α-helical transmembrane proteome. Nat Struct Mol Biol 20, 135–138 (2013). https://doi.org/10.1038/nsmb.2508

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nsmb.2508

This article is cited by

Search

Advanced search

Quick links

Nature Briefing: Translational Research

Sign up for the Nature Briefing: Translational Research newsletter — top stories in biotechnology, drug discovery and pharma.

Get what matters in translational research, free to your inbox weekly. Sign up for Nature Briefing: Translational Research