Amyloid formation of fish β-parvalbumin involves primary nucleation triggered by disulfide-bridged protein dimers.

ABSTRACT: Amyloid formation involves the conversion of soluble protein species to an aggregated state. Amyloid fibrils of β-parvalbumin, a protein abundant in fish, act as an allergen but also inhibit the in vitro assembly of the Parkinson protein α-synuclein. However, the intrinsic aggregation mechanism of β-parvalbumin has not yet been elucidated. We performed biophysical experiments in combination with mathematical modeling of aggregation kinetics and discovered that the aggregation of β-parvalbumin is initiated by the formation of dimers stabilized by disulfide bonds and then proceeds via primary nucleation and fibril elongation processes. Dimer formation is accelerated by H₂O₂ and hindered by reducing agents, resulting in faster and slower aggregation rates, respectively.

SUBMITTER: Werner TER 

PROVIDER: S-EPMC7668186 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature