The mode of α-synuclein binding to membranes depends on lipid composition and lipid to protein ratio

Interactions of the presynaptic protein alpha-synuclein with membranes are involved in its physiological action as well as in the pathological misfolding and aggregation related to Parkinsons's disease. We studied the conformation and orientation of alpha-synuclein bound to model vesicular membranes using multiparametric response polarity-sensitive fluorescent probes together with CD and EPR measurements. At low lipid to alpha-synuclein ratio the protein binds membranes through its N-terminal domain. When lipids are in excess, the alpha-helical content and the role of the C-terminus in binding increase. Highly rigid membranes also induce a greater alpha-helical content and a lower polarity of the protein microenvironment. (C) 2011 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.