Designed armadillo repeat proteins as general peptide-binding scaffolds: Consensus design and computational optimization of the hydrophobic core

TitleDesigned armadillo repeat proteins as general peptide-binding scaffolds: Consensus design and computational optimization of the hydrophobic core
Publication TypeJournal Article
Year of Publication2008
AuthorsParmeggiani F., Pellarin R., Larsen A.P, Varadamsetty G., Stumpp M.T, Zerbe O., Caflisch A., Pl├╝ckthun A.
JournalJournal of Molecular Biology
Volume376
Issue5
Pagination1282-1304
Date Published2008 Mar 7
Type of ArticleResearch Article
ISSN1089-8638
KeywordsAmino Acid Sequence, Animals, Armadillo Domain Proteins, Consensus Sequence, Databases, Protein, Escherichia coli, Humans, Hydrophobic and Hydrophilic Interactions, Mice, Models, Molecular, Molecular Sequence Data, Peptides, Protein Conformation, Protein Engineering, Protein Structure, Tertiary, Repetitive Sequences, Amino Acid, Saccharomyces cerevisiae
Abstract

Armadillo repeat proteins are abundant eukaryotic proteins involved in several cellular processes, including signaling, transport, and cytoskeletal regulation. They are characterized by an armadillo domain, composed of tandem armadillo repeats of approximately 42 amino acids, which mediates interactions with peptides or parts of proteins in extended conformation. The conserved binding mode of the peptide in extended form, observed for different targets, makes armadillo repeat proteins attractive candidates for the generation of modular peptide-binding scaffolds. Taking advantage of the large number of repeat sequences available, a consensus-based approach combined with a force field-based optimization of the hydrophobic core was used to derive soluble, highly expressed, stable, monomeric designed proteins with improved characteristics compared to natural armadillo proteins. These sequences constitute the starting point for the generation of designed armadillo repeat protein libraries for the selection of peptide binders, exploiting their modular structure and their conserved binding mode.

DOI10.1016/j.jmb.2007.12.014
pubindex

0094

Alternate JournalJ. Mol. Biol.
PubMed ID18222472
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