title: The N-terminus of α-synuclein is essential for both monomeric and oligomeric interactions with membranes.
abstract: The intrinsically disordered protein α-synuclein (αSN) is linked to Parkinson's Disease and forms both oligomeric species and amyloid fibrils. The N-terminal part of monomeric αSN interacts strongly with membranes and αSN cytotoxicity has been attributed to oligomers' ability to interact with and perturb membranes. We show that membrane folding of monomeric wt αSN and N-terminally truncated variants correlates with membrane permeabilization. Further, the first 11 N-terminal residues are crucial for monomers' and oligomers' interactions with and permeabilization of membranes. We attribute oligomer permeabilization both to cooperative electrostatic interactions through the N-terminus and interactions mediated by hydrophobic regions in the oligomer.
authors.affiliation: Interdisciplinary Nanoscience Center (iNANO), Department of Molecular Biology and Genetics, Center for Insoluble Protein Structures (inSPIN), Aarhus University, Gustav Wieds Vej 14, DK-8000 Aarhus C, Denmark.
authors.forename: Nikolai
authors.initials: N
authors.lastname: Lorenzen
authors.affiliation: Interdisciplinary Nanoscience Center (iNANO), Department of Molecular Biology and Genetics, Center for Insoluble Protein Structures (inSPIN), Aarhus University, Gustav Wieds Vej 14, DK-8000 Aarhus C, Denmark.
authors.forename: Lasse
authors.initials: L
authors.lastname: Lemminger
authors.affiliation: Interdisciplinary Nanoscience Center (iNANO), Department of Molecular Biology and Genetics, Center for Insoluble Protein Structures (inSPIN), Aarhus University, Gustav Wieds Vej 14, DK-8000 Aarhus C, Denmark.
authors.forename: Jannik Nedergaard
authors.initials: JN
authors.lastname: Pedersen
authors.affiliation: Interdisciplinary Nanoscience Center (iNANO), Department of Molecular Biology and Genetics, Center for Insoluble Protein Structures (inSPIN), Aarhus University, Gustav Wieds Vej 14, DK-8000 Aarhus C, Denmark.
authors.forename: Søren Bang
authors.initials: SB
authors.lastname: Nielsen
authors.affiliation: Interdisciplinary Nanoscience Center (iNANO), Department of Molecular Biology and Genetics, Center for Insoluble Protein Structures (inSPIN), Aarhus University, Gustav Wieds Vej 14, DK-8000 Aarhus C, Denmark. Electronic address: dao@inano.au.dk.
authors.forename: Daniel Erik
authors.initials: DE
authors.lastname: Otzen
mesh_terms: D000682:Amyloid / Q000737:chemistry* / Q000378:metabolism / Q000648:ultrastructure; D002463:Cell Membrane Permeability / Q000235:genetics; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008566:Membranes / Q000737:chemistry / Q000648:ultrastructure; D010300:Parkinson Disease / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D055503:Protein Multimerization; D020836:Protein Structure, Quaternary; D055672:Static Electricity; D051844:alpha-Synuclein / Q000737:chemistry* / Q000378:metabolism
chemical_list: D000682:Amyloid; D051844:alpha-Synuclein
keywords: 1-anilinonaphthalene-8-sulfonate; A4F; ANS; CD; DLS; Membrane folding; Membrane interaction; Oligomer; PD; Parkinson’s Disease; Permeabilization; SDS; SEC; ThT; Toxicity; asymmetrical flow field-flow fractionation; circular dichroism; dynamic light scattering; size exclusion chromatography; sodium dodecyl sulfate; thioflavin T; α-synuclein; αSN