Sequestration of a β‐Hairpin for Control of α‐Synuclein Aggregation |
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Authors: | Dr Ewa A Mirecka Hamed Shaykhalishahi Aziz Gauhar ?erife Akgül Dr Justin Lecher Prof?Dr Dieter Willbold Dr Matthias Stoldt Dr Wolfgang Hoyer |
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Institution: | 1. Institut für Physikalische Biologie, Heinrich‐Heine‐Universit?t Düsseldorf, 40204 Düsseldorf (Germany);2. Strukturbiochemie (ICS‐6), Forschungszentrum Jülich, 52425 Jülich (Germany) |
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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. |
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Keywords: | aggregation amyloids NMR spectroscopy protein engineering protein folding |
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