Projects per year
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.
Original language | English |
---|---|
Pages (from-to) | 3060-3064 |
Number of pages | 5 |
Journal | Biochemistry |
Volume | 58 |
Issue number | 28 |
Early online date | 28 Jun 2019 |
DOIs | |
Publication status | Published - 16 Jul 2019 |
Structured keywords
- BrisSynBio
- Bristol BioDesign Institute
- BCS and TECS CDTs
Keywords
- Synthetic Biology
Fingerprint Dive into the research topics of 'Stabilizing and Understanding a Miniprotein by Rational Redesign'. Together they form a unique fingerprint.
Projects
- 1 Active