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.

  • Letter
  • Published:

Solution structure of ThiS and implications for the evolutionary roots of ubiquitin

Nature Structural Biology volume 8, pages 47–51 (2001)Cite this article

Abstract

ThiS is a sulfur carrier protein that plays a central role in thiamin biosynthesis in Escherichia coli. Here we report the solution NMR structure of ThiS, the first for this class of sulfur carrier proteins. Although ThiS shares only 14% sequence identity with ubiquitin, it possesses the ubiquitin fold. This structural homology, combined with established functional similarities involving sulfur chemistry, demonstrates that the eukaryotic ubiquitin and the prokaryotic ThiS evolved from a common ancestor. This illustrates how structure determination is essential in establishing evolutionary links between proteins in which structure and function have been conserved through eons of evolution despite loss of sequence identity. The ThiS structure reveals both hydrophobic and electrostatic surface features that are likely determinants for interactions with binding partners. Comparison with surface features of ubiquitin and ubiquitin homologs SUMO-1, RUB-1 and NEDD8 suggest how Nature has utilized this single fold to incorporate similar chemistry into a broad array of highly specific biological processes.

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: Functional similarity between ubiquitin (Ub) and ThiS.
Figure 2: Solution structure determination of ThiS.
Figure 3: Tree of ubiquitin homologs.
Figure 4: Structure-function relationship between ThiS and ubiquitin.

Similar content being viewed by others

Accession codes

Accessions

Protein Data Bank

References

  1. Hershko, A. & Ciechanover, A. Annu. Rev. Biochem. 67, 425–479 ( 1998).

    Article  CAS  Google Scholar 

  2. Chen, Z.J., Parent, L. & Maniatis, T. Cell 84, 853– 862 (1996).

    Article  CAS  Google Scholar 

  3. Haas, A.L. & Siepmann, T.J. Faseb J. 11, 1257–1268 (1997).

    Article  CAS  Google Scholar 

  4. Bochtler, M., Ditzel, L., Groll, M., Hartmann, C. & Huber, R. Annu. Rev. Biophys. Biomol. Struct. 28, 295–317 (1999).

    Article  CAS  Google Scholar 

  5. Furukawa, K., Mizushima, N., Noda, T. & Ohsumi, Y. J. Biol. Chem. 275, 7462–7465 ( 2000).

    Article  CAS  Google Scholar 

  6. Jentsch, S. & Pyrowolakis, G. Trends Cell Biol. 10, 335–342 ( 2000).

    Article  CAS  Google Scholar 

  7. Hochstrasser, M. Nature Cell Biol. 2, E153–E157 (2000).

    Article  CAS  Google Scholar 

  8. Hochstrasser, M. Science 289, 563–564 ( 2000).

    Article  CAS  Google Scholar 

  9. Begley, T.P., Xi, J., Kinsland, C., Taylor, S. & McLafferty, F. Curr. Opin. Chem. Biol. 3, 623–629 (1999).

    Article  CAS  Google Scholar 

  10. Taylor, S.V. et al. J. Biol. Chem. 273, 16555– 16560 (1998).

    Article  CAS  Google Scholar 

  11. Vijay-Kumar, S., Bugg, C.E. & Cook, W.J. J. Mol. Biol. 194, 531– 544 (1987).

    Article  CAS  Google Scholar 

  12. Holm, L. & Sander, C. J. Mol. Biol. 233, 123–138 (1993).

    Article  CAS  Google Scholar 

  13. Kraulis, P.J. Science 254, 581–582 ( 1991).

    Article  CAS  Google Scholar 

  14. Tsukihara, T. et al. J. Mol. Biol. 216, 399– 410 (1990).

    Article  CAS  Google Scholar 

  15. Russell, R.B., Saqi, M.A., Sayle, R.A., Bates, P.A. & Sternberg, M.J. J. Mol. Biol. 269, 423–439 (1997).

    Article  CAS  Google Scholar 

  16. Rajagopalan, K.V. In Escherichia coli and Salmonella cellular and molecular biology, Vol. 1 (ed., Neidhardt, F.C.) 674– 686 (ASM Press, Washington, DC; 1996).

    Google Scholar 

  17. Unkles, S.E., Heck, I.S., Appleyard, M.V. & Kinghorn, J.R. J. Biol. Chem. 274, 19286–19293 (1999).

    Article  CAS  Google Scholar 

  18. Pitterle, D.M. & Rajagopalan, K.V. J Biol Chem 268, 13499–13505 ( 1993).

    CAS  PubMed  Google Scholar 

  19. Appleyard, M.V. et al. J. Biol. Chem. 273, 14869– 14876 (1998).

    Article  CAS  Google Scholar 

  20. Lo Conte, L. et al. Nucleic Acids Res. 28, 257– 259 (2000).

    Article  CAS  Google Scholar 

  21. Begley, T.P. et al. Arch. Microbiol. 171, 293– 300 (1999).

    Article  CAS  Google Scholar 

  22. Miura, T., Klaus, W., Gsell, B., Miyamoto, C. & Senn, H. J. Mol. Biol. 290, 213–228 (1999).

    Article  CAS  Google Scholar 

  23. Liu, Q. et al. J. Biol. Chem. 274, 16979– 16987 (1999).

    Article  CAS  Google Scholar 

  24. Bayer, P. et al. J. Mol. Biol. 280, 275– 286 (1998).

    Article  CAS  Google Scholar 

  25. Burch, T.J. & Haas, A.L. Biochemistry 33, 7300–7308 (1994).

    Article  CAS  Google Scholar 

  26. Kinsland, C., Taylor, S.V., Kelleher, N.L., McLafferty, F.W. & Begley, T.P. Protein Sci. 7, 1839–1842 ( 1998).

    Article  CAS  Google Scholar 

  27. Cornilescu, G., Delaglio, F. & Bax, A. J. Biomol. NMR 13, 289–302 (1999).

    Article  CAS  Google Scholar 

  28. Cavanagh, J., Fairbrother, W.J., Palmer, A.G. & Skelton, N.J. Protein NMR spectroscopy (Academic Press, San Diego, California; 1996).

    Google Scholar 

  29. Brunger, A.T. X-PLOR (Yale University, New Haven, Connecticut; 1992 ).

    Google Scholar 

  30. Kuszewski, J., Gronenborn, A.M. & Clore, G.M. Protein Sci. 5, 1067–1080 (1996).

    Article  CAS  Google Scholar 

  31. Thompson, J.D., Higgins, D.G. & Gibson, T.J. Nucleic Acids Res. 22, 4673–4680 (1994).

    Article  CAS  Google Scholar 

  32. Retief, J.D. In Bioinformatics methods and protocols, Vol. 132 (eds, Misener, S. & Krawetz, S.A.) 243 (Humana Press Inc., Totowa; 1999 ).

    Google Scholar 

  33. Dayhoff, M.O. Atlas of protein sequence and structure (National Biomedical Research foundation, Washington, DC; 1979).

    Google Scholar 

  34. Rudolph, M.J., Wuebbens, M.M., Rajagopalan, K.V. & Schindelin, H. Nature Struct. Biol. 8, 42– 46 (2000).

    Google Scholar 

Download references

Acknowledgements

We thank P.A. Karplus, R.J. MacIntyre, R.E. Oswald and R.-H. Chen for very helpful comments and discussion, L.E. Kay for use of his pulse sequence library, and F. Delaglio and D. Garrett (NIH/NIDDK) for use of their software tools. This research was funded by the NIH and the NSF. C.Wang was supported by a graduate fellowship from the Olin Foundation.

Author information

Authors and Affiliations

  1. Department of Molecular Biology and Genetics, 239 Biotechnology Building, Cornell University, Ithaca, 14853, New York, USA

    Chunyu Wang & Linda K. Nicholson

  2. Department of Chemistry and Chemical Biology, Cornell University, Ithaca, 14853, New York, USA

    Jun Xi & Tadhg P. Begley

Authors
  1. Chunyu Wang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jun Xi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Tadhg P. Begley
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Linda K. Nicholson
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Linda K. Nicholson.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Wang, C., Xi, J., Begley, T. et al. Solution structure of ThiS and implications for the evolutionary roots of ubiquitin. Nat Struct Mol Biol 8, 47–51 (2001). https://doi.org/10.1038/83041

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/83041

This article is cited by

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing