A beta-Hairpin-Binding Protein for Three Different Disease-Related Amyloidogenic Proteins

作者：Shaykhalishahi Hamed; Mirecka Ewa A; Gauhar Aziz; Gruening Clara S R; Willbold Dieter; Hard Torleif; Stoldt Matthias; Hoyer Wolfgang^*

来源：ChemBioChem, 2015, 16(3): 411-414.

DOI：10.1002/cbic.201402552

• amyloids
• intrinsically disordered proteins
• molecular recognition
• protein aggregation
• protein engineering

Amyloidogenic proteins share a propensity to convert to the beta-structure-rich amyloid state that is associated with the progression of several protein-misfolding disorders. Here we show that a single engineered beta-hairpin-binding protein, the beta-wrapin AS10, binds monomers of three different amyloidogenic proteins, that is, amyloid-beta peptide, alpha-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.

• 出版日期2015-2-9