Membrane bound α-synuclein is fully embedded in the lipid bilayer while segments with higher flexibility remain

Cellular pathways involving alpha-synuclein (alpha S) seem to be causative for development of Parkinson's disease. Interactions between alpha S and lipid membranes appear to be important for the physiological function of the protein and influence the pathological aggregation of alpha S leading to the formation of amyloid plaques. Upon membrane binding the unstructured alpha S folds into amphipathic helices. In our work we characterized the penetration depth and probed the local environment of Trp-residues introduced along the alpha S sequence. We could show that while the entire helix is well embedded in the lipid bilayer, segments with a shallower penetration and supposable higher flexibility exist. (C) 2013 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.