Structural basis for the dissociation of α-synuclein fibrils triggered by pressure perturbation of the hydrophobic core.

ABSTRACT: Parkinson's disease is a neurological disease in which aggregated forms of the α-synuclein (α-syn) protein are found. We used high hydrostatic pressure (HHP) coupled with NMR spectroscopy to study the dissociation of α-syn fibril into monomers and evaluate their structural and dynamic properties. Different dynamic properties in the non-amyloid-β component (NAC), which constitutes the Greek-key hydrophobic core, and in the acidic C-terminal region of the protein were identified by HHP NMR spectroscopy. In addition, solid-state NMR revealed subtle differences in the HHP-disturbed fibril core, providing clues to how these species contribute to seeding α-syn aggregation. These findings show how pressure can populate so far undetected α-syn species, and they lay out a roadmap for fibril dissoci

SUBMITTER: de Oliveira GA 

PROVIDER: S-EPMC5128797 | biostudies-literature | 2016 Nov

REPOSITORIES: biostudies-literature