Erratum to “Designed Armadillo Repeat Proteins: Library Generation, Characterization and Selection of Peptide Binders with High Specificity” [J. Mol. Biol. (2012) 424, 68–87]

Varadamsetty, Gautham; Tremmel, Dirk; Hansen, Simon; Parmeggiani, Fabio; Plückthun, Andreas

doi:10.1016/j.jmb.2013.01.012

Cited by 2 publications

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“…These steps were performed according to slight modifications of methods that were described previously. 25,33 Details can be found in the SI Methods.…”

Section: ■ Methodsmentioning

confidence: 99%

Structure and Energetic Contributions of a Designed Modular Peptide-Binding Protein with Picomolar Affinity

et al. 2016

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Natural armadillo repeat proteins (nArmRP) like importin-α or β-catenin bind their target peptides such that each repeat interacts with a dipeptide unit within the stretched target peptide. However, this modularity is imperfect and also restricted to short peptide stretches of usually four to six consecutive amino acids. Here we report the development and characterization of a regularized and truly modular peptide-specific binding protein, based on designed armadillo repeat proteins (dArmRP), binding to peptides of alternating lysine and arginine residues (KR)n. dArmRP were obtained from nArmRP through cycles of extensive protein engineering, which rendered them more uniform. This regularity is reflected in the consistent binding of dArmRP to (KR)-peptides, where affinities depend on the lengths of target peptides and the number of internal repeats in a very systematic manner, thus confirming the modularity of the interaction. This exponential dependency between affinity and recognition length suggests that each module adds a constant increment of binding energy to sequence-specific recognition. This relationship was confirmed by comprehensive mutagenesis studies that also reveal the importance of individual peptide side chains. The 1.83 Å resolution crystal structure of a dArmRP with five identical internal repeats in complex with the cognate (KR)5 peptide proves a modular binding mode, where each dipeptide is recognized by one internal repeat. The confirmation of this true modularity over longer peptide stretches lays the ground for the design of binders with different specificities and tailored affinities by the assembly of dipeptide-specific modules based on armadillo repeats.

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“…These steps were performed according to slight modifications of methods that were described previously. 25,33 Details can be found in the SI Methods.…”

Section: ■ Methodsmentioning

confidence: 99%

Structure and Energetic Contributions of a Designed Modular Peptide-Binding Protein with Picomolar Affinity

et al. 2016

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“…Andrea Barna (University of Zürich; on behalf of Andreas Plückthun) reported on alternatives to conventional antibodies to overcome the challenges of cross‐reactivity. She presented armadillo repeat proteins (ArmRP) as novel scaffolds for binding peptides in a modular and sequence‐specific manner . By combining computational methods with directed evolution, tight (nanomolar) and specific binders were engineered for the future generation of modular ArmRP‐based frameworks.…”

Section: De Novo Protein Designmentioning

confidence: 99%

67th Mosbacher Kolloquium: Protein Design: From First Principles to Biomedical Applications

Spieler

Lühmann

2016

ChemBioChem

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Erratum to “Designed Armadillo Repeat Proteins: Library Generation, Characterization and Selection of Peptide Binders with High Specificity” [J. Mol. Biol. (2012) 424, 68–87]

Cited by 2 publications

References 0 publications

Structure and Energetic Contributions of a Designed Modular Peptide-Binding Protein with Picomolar Affinity

Structure and Energetic Contributions of a Designed Modular Peptide-Binding Protein with Picomolar Affinity

67th Mosbacher Kolloquium: Protein Design: From First Principles to Biomedical Applications

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