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Stabilizing and Understanding a Miniprotein by Rational Redesign

Research output: Contribution to journalArticle

Original languageEnglish
Pages (from-to)3060-3064
Number of pages5
Issue number28
Early online date28 Jun 2019
DateAccepted/In press - 28 Jun 2019
DateE-pub ahead of print - 28 Jun 2019
DatePublished (current) - 16 Jul 2019


Miniproteins reduce the complexity of the protein-folding problem allowing systematic studies of contributions to protein folding and stabilization. Here, we describe the rational redesign of a miniprotein, PPα, comprising a polyproline II helix, a loop, and an α helix. The redesign provides a de novo framework for interrogating noncovalent interactions. Optimized PPα has significantly improved thermal stability with a midpoint unfolding temperature (TM) of 51 °C. Its nuclear magnetic resonance structure indicates a density of stabilizing noncovalent interactions that is higher than that of the parent peptide, specifically an increased number of CH−π interactions. In part, we attribute this to improved long-range electrostatic interactions between the two helical elements. We probe further sequence–stability relationships in the miniprotein through a series of rational mutations.

    Research areas

  • Synthetic Biology

    Structured keywords

  • BrisSynBio
  • Bristol BioDesign Institute



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