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Peptide-guided assembly of repeat protein fragments


Michel, Erich; Plückthun, Andreas; Zerbe, Oliver (2018). Peptide-guided assembly of repeat protein fragments. Angewandte Chemie Internationale Edition, 57(17):4576-4579.

Abstract

In this communication we present the peptide-guided assembly of complementary fragments of designed armadillo repeat proteins (dArmRPs) to create proteins that bind peptides not only with high affinity but also with good selectivity. We recently demonstrated that complementary N- and C-terminal fragments of dArmRPs form high-affinity complexes that resemble the structure of the full-length protein, and that these complexes bind their target peptides. We now demonstrate that dArmRPs can be split such that the fragments assemble only in the presence of a templating peptide, and that fragment mixtures enrich the combination with the highest affinity for this peptide. The enriched fragment combination discriminates single amino acid variations in the target peptide with high specificity. Our results suggest novel opportunities for the generation of new peptide binders by selection from dArmRP fragment mixtures.

Abstract

In this communication we present the peptide-guided assembly of complementary fragments of designed armadillo repeat proteins (dArmRPs) to create proteins that bind peptides not only with high affinity but also with good selectivity. We recently demonstrated that complementary N- and C-terminal fragments of dArmRPs form high-affinity complexes that resemble the structure of the full-length protein, and that these complexes bind their target peptides. We now demonstrate that dArmRPs can be split such that the fragments assemble only in the presence of a templating peptide, and that fragment mixtures enrich the combination with the highest affinity for this peptide. The enriched fragment combination discriminates single amino acid variations in the target peptide with high specificity. Our results suggest novel opportunities for the generation of new peptide binders by selection from dArmRP fragment mixtures.

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Additional indexing

Item Type:Journal Article, refereed, further contribution
Communities & Collections:04 Faculty of Medicine > Department of Biochemistry
07 Faculty of Science > Department of Biochemistry

07 Faculty of Science > Department of Chemistry
Dewey Decimal Classification:540 Chemistry
Uncontrolled Keywords:Library Armadillo Protein Fragment Peptide Binder
Language:English
Date:2018
Deposited On:16 Mar 2018 20:04
Last Modified:18 Apr 2018 11:49
Publisher:Wiley-VCH Verlag
ISSN:1433-7851
Funders:Swiss National Science Foundation, Forschungskredit Uni Zürich
Additional Information:For accepted manuscripts: This is the peer reviewed version of the following article: Michel, Erich; Plückthun, Andreas; Zerbe, Oliver (2018). Peptide-guided assembly of repeat protein fragments. Angewandte Chemie Internationale Edition:Epub ahead of print., which has been published in final form at https://doi.org/10.1002/anie.201713377. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving (http://olabout.wiley.com/WileyCDA/Section/id-820227.html#terms).
OA Status:Closed
Publisher DOI:https://doi.org/10.1002/anie.201713377
PubMed ID:29480529
Project Information:
  • : FunderSNSF
  • : Grant ID
  • : Project TitleSwiss National Science Foundation
  • : Funder
  • : Grant ID
  • : Project TitleForschungskredit Uni Zürich

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Embargo till: 2019-03-13