title: High-density lipoprotein-like particle formation of Synuclein variants.
abstract: α-Synuclein (α-Syn) is an intrinsically disordered protein in solution whose fibrillar aggregates are the hallmark of Parkinson's disease (PD). Although the specific function of α-Syn is still unclear, its high structural plasticity is key for the interactions of α-Syn with biological membranes. Recently, it has been observed that α-Syn is able to form high-density lipoprotein-like (HDL-like) particles that are reminiscent of self-assembling phospholipid bilayer nanodiscs. Here, we extended our preparation method for the production of α-Syn lipoprotein particles to the β- and γ-Syn variants, and the PD-related familial α-Syn mutants. We show that all human Syns can form stable and homogeneous populations of HDL-like particles with distinct morphologies. Our results characterize the impact of the individual Syns on the formation capacity of these particles and indicate that Syn HDL-like particles are neither causing toxicity nor a toxicity-related loss of α-Syn in PD.
authors.affiliation: In-Cell NMR Laboratory, Department of NMR-supported Structural Biology, Leibniz Institute of Molecular Pharmacology (FMP Berlin), Berlin, Germany.
authors.forename: Cédric
authors.initials: C
authors.lastname: Eichmann
authors.affiliation: Laboratory of Physical Chemistry, Swiss Federal Institute of Technology, Zürich, Switzerland.
authors.forename: Pratibha
authors.initials: P
authors.lastname: Kumari
authors.affiliation: Laboratory of Physical Chemistry, Swiss Federal Institute of Technology, Zürich, Switzerland.
authors.forename: Roland
authors.initials: R
authors.lastname: Riek
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D016632:Apolipoprotein A-I / Q000737:chemistry; D002850:Chromatography, Gel; D008075:Lipoproteins, HDL / Q000378:metabolism*; D050505:Mutant Proteins / Q000378:metabolism; D020033:Protein Isoforms / Q000378:metabolism; D017433:Protein Structure, Secondary; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D013109:Sphingomyelins / Q000378:metabolism; D034421:Sus scrofa; D051844:alpha-Synuclein / Q000737:chemistry / Q000378:metabolism*
chemical_list: D016632:Apolipoprotein A-I; D008075:Lipoproteins, HDL; D050505:Mutant Proteins; D020033:Protein Isoforms; D013109:Sphingomyelins; D051844:alpha-Synuclein
keywords: alpha Synuclein; apolipoprotein; lipid transport; membrane; neurodegenerative disease; α-Synuclein lipoprotein particles