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Publication Abstract from PubMed

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, PPalpha, comprising a polyproline II helix, a loop, and an alpha helix. The redesign provides a de novo framework for interrogating noncovalent interactions. Optimized PPalpha has significantly improved thermal stability with a midpoint unfolding temperature ( TM) of 51 degrees 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-pi 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.

Stabilizing and Understanding a Miniprotein by Rational Redesign.,Porter Goff KL, Nicol D, Williams C, Crump MP, Zieleniewski F, Samphire JL, Baker EG, Woolfson DN Biochemistry. 2019 Jul 8. doi: 10.1021/acs.biochem.9b00067. PMID:31251570^[1]

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.