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

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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.

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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
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  2. Dudley H. Williams
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  3. Leonard C. Packman
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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

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

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