title: Alpha-Synuclein Disease Mutations Are Structurally Defective and Locally Affect Membrane Binding.
abstract: The intrinsically disordered human protein alpha-Synuclein (αS) has a prominent role in Parkinson's disease (PD) pathology. Several familial variants of αS are correlated with inherited PD. Disease mutations have been shown to have an impact on lipid membrane binding. Here, using electron paramagnetic resonance spectroscopy in combination with site-directed spin labeling, we show that familial PD-associated variants are structurally defective in membrane binding and alter the local binding properties of the protein.
authors.affiliation: Department of Chemistry, Zukunftskolleg, and Konstanz Research School Chemical Biology, University of Konstanz , 78457 Konstanz, Germany.
authors.forename: Marta
authors.initials: M
authors.lastname: Robotta
authors.affiliation: Department of Chemistry, Zukunftskolleg, and Konstanz Research School Chemical Biology, University of Konstanz , 78457 Konstanz, Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Cattani
authors.affiliation: Department of Chemistry, Zukunftskolleg, and Konstanz Research School Chemical Biology, University of Konstanz , 78457 Konstanz, Germany.|Department of Physics, State University of Londrina , 86057-970 Londrina, Brazil.
authors.forename: Juliana Cristina
authors.initials: JC
authors.lastname: Martins
authors.affiliation: Department of Chemistry, Zukunftskolleg, and Konstanz Research School Chemical Biology, University of Konstanz , 78457 Konstanz, Germany.|Vrije Universiteit Amsterdam , De Boelelaan 1105, 1081 HV Amsterdam, The Netherlands.
authors.forename: Vinod
authors.initials: V
authors.lastname: Subramaniam
authors.affiliation: Department of Chemistry, Zukunftskolleg, and Konstanz Research School Chemical Biology, University of Konstanz , 78457 Konstanz, Germany.
authors.forename: Malte
authors.identifier: 0000-0002-3571-3452
authors.initials: M
authors.lastname: Drescher
mesh_terms: D001665:Binding Sites; D004578:Electron Spin Resonance Spectroscopy; D006801:Humans; D008051:Lipid Bilayers / Q000378:metabolism*; D009154:Mutation; D010300:Parkinson Disease / Q000235:genetics* / Q000378:metabolism; D051844:alpha-Synuclein / Q000235:genetics* / Q000378:metabolism
chemical_list: D008051:Lipid Bilayers; C497604:SNCA protein, human; D051844:alpha-Synuclein