title: A β-hairpin-binding protein for three different disease-related amyloidogenic proteins.
abstract: 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.
authors.affiliation: Institute of Physical Biology, Heinrich-Heine-Universität Düsseldorf, 40204 Düsseldorf (Germany).
authors.forename: Hamed
authors.initials: H
authors.lastname: Shaykhalishahi
authors.forename: Ewa A
authors.initials: EA
authors.lastname: Mirecka
authors.forename: Aziz
authors.initials: A
authors.lastname: Gauhar
authors.forename: Clara S R
authors.initials: CS
authors.lastname: Grüning
authors.forename: Dieter
authors.initials: D
authors.lastname: Willbold
authors.forename: Torleif
authors.initials: T
authors.lastname: Härd
authors.forename: Matthias
authors.initials: M
authors.lastname: Stoldt
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Hoyer
mesh_terms: D000595:Amino Acid Sequence; D016229:Amyloid beta-Peptides / Q000737:chemistry / Q000378:metabolism; D058227:Amyloidogenic Proteins / Q000737:chemistry / Q000378:metabolism*; D001665:Binding Sites; D006801:Humans; D058228:Islet Amyloid Polypeptide / Q000737:chemistry / Q000378:metabolism; D008969:Molecular Sequence Data; D019906:Nuclear Magnetic Resonance, Biomolecular; D017433:Protein Structure, Secondary; D011994:Recombinant Proteins / Q000737:chemistry / Q000378:metabolism*; D051844:alpha-Synuclein / Q000737:chemistry / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D058227:Amyloidogenic Proteins; D058228:Islet Amyloid Polypeptide; D011994:Recombinant Proteins; D051844:alpha-Synuclein
keywords: amyloids; intrinsically disordered proteins; molecular recognition; protein aggregation; protein engineering