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Publication - Professor Matthew Crump

    Stabilizing and Understanding a Miniprotein by Rational Redesign

    Citation

    Goff, KP, Nicol, D, Williams, C, Crump, M, Zieleniewski, F, Samphire, J, Baker, E & Woolfson, D, 2019, ‘Stabilizing and Understanding a Miniprotein by Rational Redesign’. Biochemistry, vol 58., pp. 3060-3064

    Abstract

    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.

    Full details in the University publications repository