Contact between the β1 and β2 Segments of α-Synuclein that Inhibits Amyloid Formation†

摘要: Conversion of the intrinsically disordered protein α-synuclein (α-syn) into amyloid aggregates is a key process in Parkinson’s disease. The sequence region 35–59 contains β-strand segments β1 and β2 α-syn fibril models most disease-related mutations. frequently engage transient interactions monomeric α-syn. consequences β1–β2 contacts are evaluated by disulfide engineering, biophysical techniques, cell viability assays. double-cysteine mutant α-synCC, with linking β2, aggregation-incompetent inhibits aggregation toxicity wild-type We show that delays amyloid-β peptide islet polypeptide involved Alzheimer’s disease type 2 diabetes, an effect enhanced α-synCC mutant. Tertiary interfere nucleation formation, suggesting promotion such as potential therapeutic approach.