TY - JOUR
T1 - Designed armadillo repeat proteins as general peptide-binding scaffolds: consensus design and computational optimization of the hydrophobic core.
AU - Parmeggiani, Fabio
AU - Pellarin, Riccardo
AU - Larsen, Anders Peter
AU - Varadamsetty, Gautham
AU - Stumpp, Michael T
AU - Zerbe, Oliver
AU - Caflisch, Amedeo
AU - Plückthun, Andreas
N1 - Keywords: Amino Acid Sequence; Animals; Armadillo Domain Proteins; Consensus Sequence; Databases, Protein; Escherichia coli; Humans; Hydrophobicity; Mice; Models, Molecular; Molecular Sequence Data; Peptides; Protein Conformation; Protein Engineering; Protein Structure, Tertiary; Repetitive Sequences, Amino Acid; Saccharomyces cerevisiae
PY - 2007
Y1 - 2007
N2 - 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.
AB - 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.
U2 - 10.1016/j.jmb.2007.12.014
DO - 10.1016/j.jmb.2007.12.014
M3 - Journal article
C2 - 18222472
SN - 0022-2836
VL - 376
SP - 1282
EP - 1304
JO - Journal of Molecular Biology
JF - Journal of Molecular Biology
IS - 5
ER -