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
Subscribe to this journal
Receive 12 print issues and online access
$209.00 per year
only $17.42 per issue
Buy this article
- Purchase on SpringerLink
- Instant access to full article PDF
Prices may be subject to local taxes which are calculated during checkout
References
Punta, M. et al. Methods 41, 460–474 (2007).
Fagerberg, L., Jonasson, K., von Heijne, G., Uhlen, M. & Berglund, L. Proteomics 10, 1141–1149 (2010).
Punta, M. et al. J. Struct. Funct. Genomics 10, 255–268 (2009).
UniProt Consortium. Nucleic Acids Res. 40, D71–D75 (2012).
Hopkins, A.L. & Groom, C.R. Nat. Rev. Drug Discov. 1, 727–730 (2002).
Giacomini, K.M. et al. Nat. Rev. Drug Discov. 9, 215–236 (2010).
Rose, P.W. et al. Nucleic Acids Res. 39, D392–D401 (2011).
Kloppmann, E., Punta, M. & Rost, B. Curr. Opin. Struct. Biol. 22, 326–332 (2012).
Hopf, T.A. et al. Cell 149, 1607–1621 (2012).
Baker, D. & Sali, A. Science 294, 93–96 (2001).
Dunbrack, R.L. Jr. Curr. Opin. Struct. Biol. 16, 374–384 (2006).
Liu, T., Tang, G.W. & Capriotti, E. Comb. Chem. High Throughput Screen. 14, 532–547 (2011).
Granseth, E., Seppala, S., Rapp, M., Daley, D.O. & Von Heijne, G. Mol. Membr. Biol. 24, 329–332 (2007).
Norvell, J.C. & Berg, J.M. Structure 15, 1519–1522 (2007).
Vitkup, D., Melamud, E., Moult, J. & Sander, C. Nat. Struct. Biol. 8, 559–566 (2001).
Marsden, R.L. & Orengo, C.A. Methods Mol. Biol. 426, 3–25 (2008).
Raftery, J. Methods Mol. Biol. 426, 37–47 (2008).
Büssow, K. et al. Microb. Cell Fact. 4, 21 (2005).
Kelly, L. et al. J. Struct. Funct. Genomics 10, 269–280 (2009).
Martí-Renom, M.A. et al. Annu. Rev. Biophys. Biomol. Struct. 29, 291–325 (2000).
Carlsson, J. et al. Nat. Chem. Biol. 7, 769–778 (2011).
Schlessinger, A. et al. Proc. Natl. Acad. Sci. USA 108, 15810–15815 (2011).
UniProt Consortium. Nucleic Acids Res. 38, D142–D148 (2010).
Vroling, B. et al. Nucleic Acids Res. 39, D309–D319 (2011).
Katritch, V., Cherezov, V. & Stevens, R.C. Trends Pharmacol. Sci. 33, 17–27 (2012).
Granier, S. et al. Nature 485, 400–404 (2012).
Schlessinger, A. et al. Protein Sci. 19, 412–428 (2010).
Mineta, K. et al. FEBS Lett. 585, 606–612 (2011).
Escudero-Esparza, A., Jiang, W.G. & Martin, T.A. Front. Biosci. 16, 1069–1083 (2011).
Angelow, S., Ahlstrom, R. & Yu, A.S. Am. J. Physiol. Renal Physiol. 295, F867–F876 (2008).
Krause, G. et al. Biochim. Biophys. Acta 1778, 631–645 (2008).
Larsson, T.P., Murray, C.G., Hill, T., Fredriksson, R. & Schioth, H.B. FEBS Lett. 579, 690–698 (2005).
Krogh, A., Larsson, B., von Heijne, G. & Sonnhammer, E.L. J. Mol. Biol. 305, 567–580 (2001).
Edgar, R.C. Bioinformatics 26, 2460–2461 (2010).
Pieper, U. et al. Nucleic Acids Res. 39, D465–D474 (2011).
Johnson, M. et al. Nucleic Acids Res. 36, W5–W9 (2008).
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
Authors and Affiliations
Corresponding authors
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
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
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1038/nsmb.2508
This article is cited by
-
Computational design of ligand-binding membrane receptors with high selectivity
Nature Chemical Biology (2017)
-
Sequence–structure relationship study in all-α transmembrane proteins using an unsupervised learning approach
Amino Acids (2015)
-
Progress in measuring biophysical properties of membrane proteins with AFM single-molecule force spectroscopy
Chinese Science Bulletin (2014)