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Stabilizing and Understanding a Miniprotein by Rational Redesign

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Stabilizing and Understanding a Miniprotein by Rational Redesign. / Porter Goff, Kathryn; Nicol, Debbie; Williams, Christopher; Crump, Matthew; Zieleniewski, Francis; Samphire, Jennifer; Baker, Emily; Woolfson, Derek.

In: Biochemistry, Vol. 58, No. 28, 16.07.2019, p. 3060-3064.

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@article{a6102cecf03a48f6923f403f29c502a1,
title = "Stabilizing and Understanding a Miniprotein by Rational Redesign",
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.",
keywords = "Synthetic Biology",
author = "{Porter Goff}, Kathryn and Debbie Nicol and Christopher Williams and Matthew Crump and Francis Zieleniewski and Jennifer Samphire and Emily Baker and Derek Woolfson",
year = "2019",
month = "7",
day = "16",
doi = "10.1021/acs.biochem.9b00067",
language = "English",
volume = "58",
pages = "3060--3064",
journal = "Biochemistry",
issn = "0006-2960",
publisher = "American Chemical Society",
number = "28",

}

RIS - suitable for import to EndNote

TY - JOUR

T1 - Stabilizing and Understanding a Miniprotein by Rational Redesign

AU - Porter Goff, Kathryn

AU - Nicol, Debbie

AU - Williams, Christopher

AU - Crump, Matthew

AU - Zieleniewski, Francis

AU - Samphire, Jennifer

AU - Baker, Emily

AU - Woolfson, Derek

PY - 2019/7/16

Y1 - 2019/7/16

N2 - 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.

AB - 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.

KW - Synthetic Biology

UR - http://www.scopus.com/inward/record.url?scp=85069849699&partnerID=8YFLogxK

U2 - 10.1021/acs.biochem.9b00067

DO - 10.1021/acs.biochem.9b00067

M3 - Article

C2 - 31251570

AN - SCOPUS:85069849699

VL - 58

SP - 3060

EP - 3064

JO - Biochemistry

JF - Biochemistry

SN - 0006-2960

IS - 28

ER -