The aggregation and membrane-binding properties of an α-synuclein peptide fragment

α-Synuclein is a 140 amino acid protein, which is associated with presynaptic membranes in the brain, and is the major component of protein aggregates produced during the progression of many neurodegenerative diseases. It has been shown that a central hydrophobic region of α-synuclein comprising residues 71–82 is required for aggregation of the protein into the fibrillar form found in pathogenic aggregates [Giasson, Murray, Trojanowski and Lee (2001) J. Biol. Chem. 276, 2380–2386]. In the present study, we used ²H NMR and electron microscopy to investigate the aggregation and membrane-binding properties of a synthetic peptide corresponding to this region. Results indicate that this region associates with phospholipid bilayers but also forms amyloid-like fibrils in the absence of lipid membranes.