title: Sequestration of a β-hairpin for control of α-synuclein aggregation.
abstract: The misfolding and aggregation of the protein α-synuclein (α-syn), which results in the formation of amyloid fibrils, is involved in the pathogenesis of Parkinson's disease and other synucleinopathies. The emergence of amyloid toxicity is associated with the formation of partially folded aggregation intermediates. Here, we engineered a class of binding proteins termed β-wrapins (β-wrap proteins) with affinity for α-synuclein (α-syn). The NMR structure of an α-syn:β-wrapin complex reveals a β-hairpin of α-syn comprising the sequence region α-syn(37-54). The β-wrapin inhibits α-syn aggregation and toxicity at substoichiometric concentrations, demonstrating that it interferes with the nucleation of aggregation.
authors.affiliation: Institut für Physikalische Biologie, Heinrich-Heine-Universität Düsseldorf, 40204 Düsseldorf (Germany).
authors.forename: Ewa A
authors.initials: EA
authors.lastname: Mirecka
authors.forename: Hamed
authors.initials: H
authors.lastname: Shaykhalishahi
authors.forename: Aziz
authors.initials: A
authors.lastname: Gauhar
authors.forename: Şerife
authors.initials: Ş
authors.lastname: Akgül
authors.forename: Justin
authors.initials: J
authors.lastname: Lecher
authors.forename: Dieter
authors.initials: D
authors.lastname: Willbold
authors.forename: Matthias
authors.initials: M
authors.lastname: Stoldt
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Hoyer
mesh_terms: D000595:Amino Acid Sequence; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D010300:Parkinson Disease / Q000378:metabolism; D015202:Protein Engineering; D017510:Protein Folding; D017433:Protein Structure, Secondary; D051844:alpha-Synuclein / Q000737:chemistry*
chemical_list: D051844:alpha-Synuclein
keywords: NMR spectroscopy; aggregation; amyloids; protein engineering; protein folding