title: Alpha-synuclein pore forming activity upon membrane association.
abstract: Alpha-synuclein is a natively unfolded protein widely expressed in neurons at the presynaptic level. It is linked to Parkinson's disease by two lines of evidence: amyloid fibrils of the protein accumulate in patients' brains and three genetic mutants cause autosomal dominant forms of the disease. The biological role of the protein and the mechanisms involved in the etiopathogenesis of Parkinson's disease are still unknown. Membrane binding causes the formation of an amphipathic alpha-helix, which lies on the surface without crossing the bilayer. Recent observations however reported that the application of a voltage induces a pore-like activity of alpha-synuclein. This study aims to characterize the pore forming activity of the protein starting from its monomeric form. In particular, experiments with planar lipid membranes allowed recording of conductance activity bursts with a defined and reproducible fingerprint. Additional experiments with deletion mutants and covalently bound alpha-synuclein dimers were performed to understand both pore assembly and stoichiometry. The information acquired allowed formulation of a model for pore formation at different conductance levels.
authors: Istituto di Biofisica, Consiglio Nazionale delle Ricerche & Fondazione Bruno Kessler, Trento, Italy.
authors: Laura
authors: L
authors: Tosatto
authors: Alberto O
authors: AO
authors: Andrighetti
authors: Nicoletta
authors: N
authors: Plotegher
authors: Valeria
authors: V
authors: Antonini
authors: Isabella
authors: I
authors: Tessari
authors: Leonardo
authors: L
authors: Ricci
authors: Luigi
authors: L
authors: Bubacco
authors: Mauro
authors: M
authors: Dalla Serra
mesh_terms: D002462:Cell Membrane / Q000378:metabolism; D019281:Dimerization; D008051:Lipid Bilayers; D051844:alpha-Synuclein / Q000378:metabolism*
chemical_list: D008051:Lipid Bilayers; D051844:alpha-Synuclein