Peptide-Guided Assembly of Repeat Protein Fragments

Angewandte Chemie
Erich MichelOliver Zerbe

Abstract

Herein, 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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Citations

Dec 6, 2018·Biological Chemistry·Erich MichelOliver Zerbe
Mar 16, 2021·Current Opinion in Structural Biology·Frances Gidley, Fabio Parmeggiani
Jun 3, 2021·Proceedings of the National Academy of Sciences of the United States of America·Ivan VulovicDavid Baker
Aug 3, 2021·Journal of Biomolecular NMR·Stefano CucuzzaOliver Zerbe

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