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.

  • Article
  • Published:

A short linear peptide derived from the N-terminal sequence of ubiquitin folds into a water-stable non-native β-hairpin

Nature Structural Biology volume 2, pages 999–1006 (1995)Cite this article

Abstract

A 16-residue peptide derived from the N-terminal sequence of ubiquitin forms a stable monomeric β-hairpin that is estimated to be ∼80% populated in aqueous solution. The peptide sequence has been modified from native ubiquitin by replacing the five residues found in a type IG1 bulged turn (Thr-Leu-Thr-Gly-Lys) with four residues (Asn-Pro-Asp-Gly) to maximize the probability of forming a β-turn. Unexpectedly, the bulged turn conformation is re-established in the β-hairpin in solution with two consequences: a one-amino acid frame-shift in the alignment of the peptide main chain occurs relative to the native hairpin, and side chains formerly on opposite faces of the hairpin are brought together on the same face. The presence of the bulged turn in native ubiquitin may help in the avoidance of the stable non-native register of amino acids found here which would be unproductive for folding.

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

Similar content being viewed by others

References

  1. Wright, P.E., Dyson, H.J. & Lerner, R.A. Conformation of peptide fragments of proteins in aqueous solution: implications for initiation of protein folding. Biochemistry 27, 7167–7175 (1988).

    Article  CAS  Google Scholar 

  2. Dobson, C.M., Evans, P.A. & Radford, S.E. Understanding how proteins fold: the lysozyme story so far. Trends biochem. Sci. 19, 31–37 (1994).

    Article  CAS  Google Scholar 

  3. Dill, K.A. Dominant forces in protein folding. Biochemistry 29, 7133–7155 (1990).

    Article  CAS  Google Scholar 

  4. Dyson, H.J. & Wringht, R.E. Peptide conformation and protein folding. Curr. Opin. struct. Biol. 3, 60–65 (1993).

    Article  CAS  Google Scholar 

  5. Dyson, H.J., Merutka, G., Waltho, J.P., Lerner, R.A. & Wright, P.E. Folding of peptide fragments comprising the complete sequence of proteins. Models for initiation of protein folding II. Myohemerythrin. J. molec. Biol. 226, 795–817 (1992).

    Article  CAS  Google Scholar 

  6. Baldwin, R.L. Seeding protein folding. Trends biochem. Sci. 11, 6–9 (1986).

    Article  CAS  Google Scholar 

  7. DeGrado, W.F. Design of peptides and proteins. Adv. Protein. Chem. 39, 51–124 (1988).

    Article  CAS  Google Scholar 

  8. DeGrado, W.F. & Matthews, B.W. Engineering and design. Curr. Opin. struct. Biol. 3, 547–548 (1993).

    Article  Google Scholar 

  9. Blanco, F.J., Rivas, G. & Serrano, L. A short linear peptide that folds into a native stable β-hairpin in aqueous solution. Nature struct. Biol. 1, 584–590(1994).

    Article  CAS  Google Scholar 

  10. Blanco, F.J. et al. Evidence of a short linear peptide that folds into a β-hairpin in aqueous solution. J. Am. chem. Soc. 115, 5887–5888 (1993).

    Article  CAS  Google Scholar 

  11. Blanco, F.J. et al. NMR solution structure of the isolated N-terminal fragment of protein G B1 Domain. Evidence of TFE induced native-like β-hairpin formation. Biochemistry 33, 6004–6014 (1994).

    Article  CAS  Google Scholar 

  12. Cox, J.P.L., Evans, P.A., Packman, L.C., Williams, D.H. & Woolfson, D.N. Dissecting the structure of a partially folded protein: circular dichroism and nuclear magnetic resonance studies of peptides from ubiquitin. J. molec. Biol. 234, 483–492 (1993).

    Article  CAS  Google Scholar 

  13. Harding, M.M., Williams, D.H. & Woolfson, D.N. Characterisation of a partially denatured state of a protein by two dimensional NMR: reduction of the hydrophobic interaction in ubiquitin. Biochemistry 30, 3120–3128 (1991).

    Article  CAS  Google Scholar 

  14. Vijay-Kumar, S., Bugg, C.E. & Cook, W.J. Structure of ubiquitin refined at 1.8 Å resolution. J. molec. Biol. 194, 531–544 (1986).

    Article  Google Scholar 

  15. Wilmot, C.M. & Thornton, J.M. Analysis and prediction of the different types of β-turn in proteins. J. molec. Biol. 203, 221–232 (1988).

    Article  CAS  Google Scholar 

  16. Dyson, H.J. & Wright, P.E. Defining solution conformations of short linear peptides. A. Rev. biophys. Biochem. 20, 519–538 (1991).

    CAS  Google Scholar 

  17. Wishart, D.S., Sykes, B.D. & Richards, F.M. The chemical shift index: a fast and simple method for assignment of protein secondary structure through NMR spectroscopy. Biochemistry 31, 1647–1651 (1992).

    Article  CAS  Google Scholar 

  18. Bundi, A. & Wuthrich, K. 1H NMR parameters of the common amino acid residues measured in aqueous solutions of linear tetrapeptides H-Gly-Gly-X-L-AlaOH. Biopolymers 18, 285–296 (1979).

    Article  CAS  Google Scholar 

  19. Chothia, C.H. Hydrophobic bonding and accessible surface areas in proteins. Nature 248, 338–339 (1974).

    Article  CAS  Google Scholar 

  20. Padmanabhan, S., Baldwin, R.L. Helix stabilising interactions between tyrosine and leucine or valine when spacing is i,i+4. J. molec. Biol. 241, 706–713 (1994).

    Article  CAS  Google Scholar 

  21. Woolfson, D.N., Cooper, A., Harding, M.M., Williams, D.H. & Evans, P.A. Protein folding in the absence of the solvent ordering component to the hydrophobic interaction. J. molec. Biol. 229, 502–511 (1993).

    Article  CAS  Google Scholar 

  22. Minor, D.L. Jr. & Kim, P.S. Measurement of the β-sheet forming propensities of amino acids. Nature 367, 660–663 (1994).

    Article  CAS  Google Scholar 

  23. Minor, D.L. Jr. & Kim, P.S. Context is a major determinant of β-sheet propensity. Nature 371, 264–267 (1994).

    Article  CAS  Google Scholar 

  24. Sibanda, B.L., Blundell, T.L. & Thornton, J.M. Conformation of β-hairpins in protein structures. A systematic classification with applications to modelling by homology, electron density fitting and protein engineering. J. molec. Biol. 206, 759–777 (1989).

    Article  CAS  Google Scholar 

  25. Mohamadi, F. et al. MacroModel – an integrated software system for modelling organic and biorganic molecules using molecular mechanics. J. comput. Chem. 11, 440–467 (1990).

    Article  CAS  Google Scholar 

  26. Kraulis, P.J. Molscript: a program to produce both detailed and schematic plots of protein structures. J. appl. Crystallogr. 24, 946–950 (1991).

    Article  Google Scholar 

Download references

Author information

Author notes

  1. Mark S. Searle

    Present address: Department of Chemistry, University Park, Nottingham, NG7 2RD, UK

Authors and Affiliations

  1. Cambridge Centre for Molecular Recognition, University Chemical Laboratories, Lensfield Road, Cambridge, CB2 1EW, UK

    Mark S. Searle & Dudley H. Williams

  2. Cambridge Centre for Molecular Recognition, Department of Biochemistry, Tennis Court Road, Cambridge, CB2 1QW, UK

    Leonard C. Packman

Authors
  1. Mark S. Searle
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Dudley H. Williams
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Leonard C. Packman
    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

Searle, M., Williams, D. & Packman, L. A short linear peptide derived from the N-terminal sequence of ubiquitin folds into a water-stable non-native β-hairpin. Nat Struct Mol Biol 2, 999–1006 (1995). https://doi.org/10.1038/nsb1195-999

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nsb1195-999

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