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

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.

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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.).

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

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

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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

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