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Post-reductionist protein science, or putting Humpty Dumpty back together again

Nature Chemical Biology volume 5, pages 774–777 (2009)Cite this article

In their native environments, proteins perform their biological roles in highly concentrated viscous solutions and in complex networks with numerous partners. Yet for many years, the normal practice has been to purify a protein of interest in order to characterize its structural and functional properties. In this Commentary, we discuss how protein scientists are now tackling the theoretical and methodological challenges of studying proteins in their physiological context.

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Figure 1: A cross-section of a bacterial cell.
Figure 2: Examples of powerful new methods to study proteins in their native environments, networks and complexes.

References

  1. Zhou, H.X., Rivas, G. & Minton, A.P. Annu. Rev. Biophys. 37, 375–397 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. Dix, J.A. & Verkman, A.S. Annu. Rev. Biophys. 37, 247–263 (2008).

    Article  CAS  PubMed  Google Scholar 

  3. Pielak, G.J. et al. Biochemistry 48, 226–234 (2009).

    Article  CAS  PubMed  Google Scholar 

  4. Serber, Z., Corsini, L., Durst, F. & Dötsch, V. Methods Enzymol. 394, 17–41 (2005).

    Article  CAS  PubMed  Google Scholar 

  5. Srere, P.A. Trends Biochem. Sci. 25, 150–153 (2000).

    Article  CAS  PubMed  Google Scholar 

  6. McConkey, E.H. Proc. Natl. Acad. Sci. USA 79, 3236–3240 (1982).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Durek, P. & Walther, D. BMC Syst. Biol. 2, 100 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  8. Alberts, B. Cell 92, 291–294 (1998).

    Article  CAS  PubMed  Google Scholar 

  9. Kempner, E.S. & Miller, J.H. Cell Motil. Cytoskeleton 56, 219–224 (2003).

    Article  CAS  PubMed  Google Scholar 

  10. Misteli, T. Cell 128, 787–800 (2007).

    Article  CAS  PubMed  Google Scholar 

  11. Lippincott-Schwartz, J., Roberts, T.H. & Hirschberg, K. Annu. Rev. Cell Dev. Biol. 16, 557–589 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Zhang, J., Maslov, S. & Shakhnovich, E.I. Mol. Syst. Biol. 4, 210 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  13. Wilt, B.A. et al. Annu. Rev. Neurosci. 32, 435–506 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Hoenger, A. & McIntosh, J.R. Curr. Opin. Cell Biol. 21, 89–96 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Brandt, F. et al. Cell 136, 261–271 (2009).

    Article  CAS  PubMed  Google Scholar 

  16. Elcock, A.H. PLoS Comput. Biol. 2, e98 (2006).

    Article  PubMed  PubMed Central  Google Scholar 

  17. Alber, F., Forster, F., Korkin, D., Topf, M. & Sali, A. Annu. Rev. Biochem. 77, 443–477 (2008).

    Article  CAS  PubMed  Google Scholar 

  18. Stein, M., Gabdoulline, R.R. & Wade, R.C. Curr. Opin. Struct. Biol. 17, 166–172 (2007).

    Article  CAS  PubMed  Google Scholar 

  19. Bader, S., Kuhner, S. & Gavin, A.C. FEBS Lett. 582, 1220–1224 (2008).

    Article  CAS  PubMed  Google Scholar 

  20. Puig, O. et al. Methods 24, 218–229 (2001).

    Article  CAS  PubMed  Google Scholar 

  21. Remy, I. & Michnick, S.W. Methods Mol. Biol. 261, 411–426 (2004).

    CAS  PubMed  Google Scholar 

  22. Fields, S. & Sternglanz, R. Trends Genet. 10, 286–292 (1994).

    Article  CAS  PubMed  Google Scholar 

  23. Collins, S.R., Schuldiner, M., Krogan, N.J. & Weissman, J.S. Genome Biol. 7, R63 (2006).

    Article  PubMed  PubMed Central  Google Scholar 

  24. Roguev, A. et al. Science 322, 405–410 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Sykes, M.T. & Williamson, J.R. Annu. Rev. Biophys. 38, 197–215 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Adilakshmi, T., Lease, R.A. & Woodson, S.A. Nucleic Acids Res. 34, e64 (2006).

    Article  PubMed  PubMed Central  Google Scholar 

  27. Sharon, M. & Robinson, C.V. Annu. Rev. Biochem. 76, 167–193 (2007).

    Article  CAS  PubMed  Google Scholar 

  28. Bennett, B.D. et al. Nat. Chem. Biol. 5, 593–599 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Gutstein, H.B., Morris, J.S., Annangudi, S.P. & Sweedler, J.V. Mass Spectrom. Rev. 27, 316–330 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Specht, K.M. & Shokat, K.M. Curr. Opin. Cell Biol. 14, 155–159 (2002).

    Article  CAS  PubMed  Google Scholar 

  31. Xie, X.S., Choi, P.J., Li, G.W., Lee, N.K. & Lia, G. Annu. Rev. Biophys. 37, 417–444 (2008).

    Article  CAS  PubMed  Google Scholar 

  32. Werner, J.N. et al. Proc. Natl. Acad. Sci. USA 106, 7858–7863 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Greenfield, D. et al. PLoS Biol. 7, e1000137 (2009).

    Article  PubMed  PubMed Central  Google Scholar 

  34. Ignatova, Z. et al. Biopolymers 88, 157–163 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Butland, G. et al. Nature 433, 531–537 (2005).

    Article  CAS  PubMed  Google Scholar 

Download references

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Authors and Affiliations

  1. Lila M. Gierasch is in the Department of Biochemistry and Molecular Biology and the Department of Chemistry, University of Massachusetts, Amherst, Amherst, Massachusetts, USA, and,

    Lila M Gierasch

  2. Anne Gershenson is in the Department of Biochemistry and Molecular Biology, University of Massachusetts, Amherst, Amherst, Massachusetts, USA.,

    Anne Gershenson

Authors
  1. Lila M Gierasch
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  2. Anne Gershenson
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Correspondence to Lila M Gierasch or Anne Gershenson.

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Gierasch, L., Gershenson, A. Post-reductionist protein science, or putting Humpty Dumpty back together again. Nat Chem Biol 5, 774–777 (2009). https://doi.org/10.1038/nchembio.241

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