title: Remodeling of lipid vesicles into cylindrical micelles by α-synuclein in an extended α-helical conformation.
abstract: α-Synuclein (αS) is a protein with multiple conformations and interactions. Natively unfolded in solution, αS accumulates as amyloid in neurological tissue in Parkinson disease and interacts with membranes under both physiological and pathological conditions. Here, we used cryoelectron microscopy in conjunction with electron paramagnetic resonance (EPR) and other techniques to characterize the ability of αS to remodel vesicles. At molar ratios of 1:5 to 1:40 for protein/lipid (1-palmitoyl-2-oleoyl-sn-glycero-3-phosphoglycerol), large spherical vesicles are converted into cylindrical micelles ~50 Å in diameter. Other lipids of the same charge (negative) exhibit generally similar behavior, although bilayer tubes of 150-500 Å in width are also produced, depending on the lipid acyl chains. At higher protein/lipid ratios, discoid particles, 70-100 Å across, are formed. EPR data show that, on cylindrical micelles, αS adopts an extended amphipathic α-helical conformation, with its long axis aligned with the tube axis. The observed geometrical relationship between αS and the micelle suggests that the wedging of its long α-helix into the outer leaflet of a membrane may cause curvature and an anisotropic partition of lipids, leading to tube formation.
authors: Laboratory of Structural Biology, NIAMS, National Institutes of Health, Bethesda, MD 20892, USA. mizuno@biochem.mpg.de
authors: Naoko
authors: N
authors: Mizuno
authors: Jobin
authors: J
authors: Varkey
authors: Natalie C
authors: NC
authors: Kegulian
authors: Balachandra G
authors: BG
authors: Hegde
authors: Naiqian
authors: N
authors: Cheng
authors: Ralf
authors: R
authors: Langen
authors: Alasdair C
authors: AC
authors: Steven
mesh_terms: D004578:Electron Spin Resonance Spectroscopy; D006801:Humans; D008051:Lipid Bilayers / Q000737:chemistry* / Q000378:metabolism; D008823:Micelles; D010300:Parkinson Disease / Q000235:genetics / Q000378:metabolism; D010715:Phosphatidylglycerols / Q000737:chemistry* / Q000378:metabolism; D017510:Protein Folding; D017433:Protein Structure, Secondary; D051844:alpha-Synuclein / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism
chemical_list: D008051:Lipid Bilayers; D008823:Micelles; D010715:Phosphatidylglycerols; D051844:alpha-Synuclein; C060037:1-palmitoyl-2-oleoylglycero-3-phosphoglycerol