A β‐Hairpin‐Binding Protein for Three Different Disease‐Related Amyloidogenic Proteins

Amyloidogenic proteins share a propensity to convert to the β‐structure‐rich amyloid state that is associated with the progression of several protein‐misfolding disorders. Here we show that a single engineered β‐hairpin‐binding protein, the β‐wrapin AS10, binds monomers of three different amyloidogenic proteins, that is, amyloid‐β peptide, α‐synuclein, and islet amyloid polypeptide, with sub‐micromolar affinity. AS10 binding inhibits the aggregation and toxicity of all three proteins. The results demonstrate common conformational preferences and related binding sites in a subset of the amyloidogenic proteins. These commonalities enable the generation of multispecific monomer‐binding agents.