title: α-Synuclein-induced tubule formation in lipid bilayers.
abstract: α-Synuclein is a presynaptic protein that binds to phospholipid membranes and is involved in the pathogenesis of Parkinson's disease (PD). In this paper, we describe the effects of adding wild-type α-synuclein (WT) and three familial PD mutants (A53T, A30P, and E46K) to membranes containing 15-35 mol % anionic lipid. Tubules were observed to form in the membranes to an extent that depended on the α-synuclein variant, the anionic lipid content, and the protein concentration. For all four variants, tubule formation decreased with increasing anionic lipid content. Tubules were more readily observed with A30P and E46K than with WT or A53T. The results are consistent with a model wherein the helical content of α-synuclein increases with increasing anionic lipid content, and α-synuclein conformers with low helical content have a high propensity to induce tubule formation. This work, combined with previous work from our laboratory (Pandey et al. Biophys. J. 2009, 96, 540), shows that WT adsorption of the protein has deleterious effects on the membrane when the anionic lipid concentration is less than 30 mol % (tubule formation) or greater than 40 mol % (reorganization of the bilayer, clustering of protein).
authors.affiliation: Department of Chemistry, Purdue University, West Lafayette, Indiana 47907, USA.
authors.forename: Anjan P
authors.initials: AP
authors.lastname: Pandey
authors.forename: Farzin
authors.initials: F
authors.lastname: Haque
authors.forename: Jean-Christophe
authors.initials: JC
authors.lastname: Rochet
authors.forename: Jennifer S
authors.initials: JS
authors.lastname: Hovis
mesh_terms: D019943:Amino Acid Substitution; D006801:Humans; D008051:Lipid Bilayers / Q000737:chemistry*; D009154:Mutation; D010300:Parkinson Disease / Q000378:metabolism; D011485:Protein Binding; D011994:Recombinant Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D051844:alpha-Synuclein / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: D008051:Lipid Bilayers; D011994:Recombinant Proteins; D051844:alpha-Synuclein