Skip to main content

Advertisement

SpringerLink
Log in

The integration of cell and chemical biology in protein folding

  • Commentary
  • Published:

From Nature Chemical Biology

View current issue Submit your manuscript

Eukaryotic cells are specialized, interdependent functional units of complex tissues that are composed of metabolically integrated systems defined by chemically distinct organelles that operate as reaction vessels. It is now clear that the small-molecule and polymer-based composition of these organelles plays a crucial role in generating and maintaining protein folds and functions through the systems chemistry of the local environments.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Figure 1: The chemical environments of eukaryotic exocytic and endocytic pathways.
Figure 2: Protein folding energy surfaces representing a square slice from the folding funnel in vitro and in vivo.

References

  1. Bonifacino, J.S. & Glick, B.S. Cell 116, 153–166 (2004).

    Article  CAS  Google Scholar 

  2. Young, J.C., Agashe, V.R., Siegers, K. & Hartl, F.U. Nat. Rev. Mol. Cell Biol. 5, 781–791 (2004).

    Article  CAS  Google Scholar 

  3. Onuchic, J.N. & Wolynes, P.G. Curr. Opin. Struct. Biol. 14, 70–75 (2004).

    Article  CAS  Google Scholar 

  4. Huff, M.E., Page, L.J., Balch, W.E. & Kelly, J.W. Gelsolin domain 2 Ca2+ affinity determines susceptibility to furin proteolysis and familial amyloidosis of finnish type. J. Mol. Biol. 334, 119–127 (2003).

    Article  CAS  Google Scholar 

  5. Sawkar, A.R. et al. Chemical chaperones increase the cellular activity of N370S beta -glucosidase: a therapeutic strategy for Gaucher disease. Proc. Natl. Acad. Sci. USA 99, 15428–15433 (2002).

    Article  CAS  Google Scholar 

  6. Albanese, V., Yam, A.Y., Baughman, J., Parnot, C. & Frydman, J. Cell 124, 75–88 (2006).

    Article  CAS  Google Scholar 

  7. Young, J.C., Barral, J.M. & Ulrich Hartl, F. Trends Biochem. Sci. 28, 541–547 (2003).

    Article  CAS  Google Scholar 

  8. Cohen, E., Bieschke, J., Perciavalle, R., Kelly, J.W. & Dillin, A. Science (in the press) (2006).

    Google Scholar 

  9. Gidalevitz, T., Ben-Zvi, A., Ho, K.H., Brignull, H.R. & Morimoto, R.I. Science 311, 1471–1474 (2006).

    Article  CAS  Google Scholar 

  10. Morley, J.F. & Morimoto, R.I. Mol. Biol. Cell 15, 657–664 (2004).

    Article  CAS  Google Scholar 

  11. Schroder, M. & Kaufman, R.J. Annu. Rev. Biochem. 74, 739–789 (2005).

    Article  Google Scholar 

  12. Spiess, C., Meyer, A.S., Reissmann, S. & Frydman, J. Mechanism of the eukaryotic chaperonin: protein folding in the chamber of secrets. Trends Cell Biol. 14, 598–604 (2004).

    Article  CAS  Google Scholar 

  13. Lundbaek, J.A., Andersen, O.S., Werge, T. & Nielsen, C. Biophys. J. 84, 2080–2089 (2003).

    Article  CAS  Google Scholar 

  14. Helenius, A. & Aebi, M. Annu. Rev. Biochem. 73, 1019–1049 (2004).

    Article  CAS  Google Scholar 

  15. Allan, B.B. & Balch, W.E. Science 285, 63–66 (1999).

    Article  CAS  Google Scholar 

  16. Storrie, B. Int. Rev. Cytol. 244, 69–94 (2005).

    Article  CAS  Google Scholar 

  17. Kaeser, P.S. & Sudhof, T.C. Biochem. Soc. Trans. 33, 1345–1349 (2005).

    Article  CAS  Google Scholar 

  18. Molinete, M., Irminger, J.C., Tooze, S.A. & Halban, P.A. Semin. Cell Dev. Biol. 11, 243–251 (2000).

    Article  CAS  Google Scholar 

  19. Rorsman, P. & Renstrom, E. Diabetologia 46, 1029–1045 (2003).

    Article  CAS  Google Scholar 

  20. Fowler, D.M. et al. PLoS Biol. 4, e6 (2006).

    Article  Google Scholar 

  21. Conner, S.D. & Schmid, S.L. Nature 422, 37–44 (2003).

    Article  CAS  Google Scholar 

  22. Hla, T. Prostaglandins Other Lipid Mediat. 77, 197–209 (2005).

    Article  CAS  Google Scholar 

  23. Hill, S.J. Br. J. Pharmacol. 147 (Suppl 1.), S27–S37 (2006).

    CAS  PubMed  PubMed Central  Google Scholar 

  24. Aridor, M. & Balch, W.E. Nat. Med. 5, 745–751 (1999).

    Article  CAS  Google Scholar 

  25. Moyer, B.D. & Balch, W.E. Expert Opin. Ther. Targets 5, 165–176 (2001).

    CAS  PubMed  Google Scholar 

  26. Ulloa-Aguirre, A., Janovick, J.A., Brothers, S.P. & Conn, P.M. Traffic 5, 821–837 (2004).

    Article  CAS  Google Scholar 

  27. Brady, R.O. Annu. Rev. Med. 57, 283–296 (2006).

    Article  CAS  Google Scholar 

  28. Gadsby, D.C., Vergani, P. & Csanady, L. Nature 440, 477–483 (2006).

    Article  CAS  Google Scholar 

  29. Lomas, D.A. et al. Biochem. Soc. Trans. 33, 321–330 (2005).

    Article  CAS  Google Scholar 

  30. Buxbaum, J.N. & Tagoe, C.E. Annu. Rev. Med. 51, 543–569 (2000).

    Article  CAS  Google Scholar 

  31. Sekijima, Y. et al. Cell 121, 73–85 (2005).

    Article  CAS  Google Scholar 

  32. Sawkar, A.R. et al. Chem. Biol. 12, 1235–1244 (2005).

    Article  CAS  Google Scholar 

  33. Pedemonte, N. et al. J. Clin. Invest. 115, 2564–2571 (2005).

    Article  CAS  Google Scholar 

  34. Van Goor, F. et al. 2006. Am. J. Physiol. Lung Cell. Mol. Physiol., published online 27 January 2006 (doi:10.1152/ajplung.00169.2005).

  35. Hammarstrom, P., Wiseman, R.L., Powers, E.T. & Kelly, J.W. Science 299, 713–716 (2003).

    Article  Google Scholar 

  36. Saghatelian, A. & Cravatt, B.F. Global strategies to integrate the proteome and metabolome. Curr. Opin. Chem. Biol. 9, 62–68 (2005).

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by US National Institutes of Health grants GM42336 to W.E.B. and AG18917 and DK46335 to J.W.K. and by the Lita Annenberg Hazen Foundation (J.W.K.) and Cystic Fibrosis Foundation (W.E.B.).

Author information

Authors and Affiliations

  1. Department of Chemistry and The Skaggs Institute for Chemical Biology,

    Jeffery W Kelly & William E Balch

  2. Department of Cell Biology and The Institute for Childhood and Neglected Disease, The Scripps Research Institute, 10550 N. Torrey Pines Road, La Jolla, 92130, California, USA

    Jeffery W Kelly & William E Balch

Authors
  1. Jeffery W Kelly
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. William E Balch
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Kelly, J., Balch, W. The integration of cell and chemical biology in protein folding. Nat Chem Biol 2, 224–227 (2006). https://doi.org/10.1038/nchembio0506-224

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/nchembio0506-224

  • Springer Nature America, Inc.

This article is cited by

Search

Navigation