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.
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Titolo: | Alpha-synuclein pore forming activity upon membrane association |
Autori: | Tosatto, L.; Andrighetti, A. O.; Plotegher, N.; Antonini, V.; Tessari, I.; Ricci, Leonardo; Bubacco, L.; Dalla Serra, Mauro |
Autori Unitn: | |
Titolo del periodico: | BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES |
Anno di pubblicazione: | 2012 |
Numero e parte del fascicolo: | 11 |
Codice identificativo Scopus: | 2-s2.0-84864771992 |
Codice identificativo Pubmed: | 22820150 |
Codice identificativo ISI: | WOS:000309081700042 |
Digital Object Identifier (DOI): | http://dx.doi.org/10.1016/j.bbamem.2012.07.007 |
Handle: | http://hdl.handle.net/11572/95266 |
Appare nelle tipologie: | 03.1 Articolo su rivista (Journal article) |
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BiochimicaBiophysicaActa_2012_1818_2876.pdf | Post-print referato (Refereed author’s manuscript) | Tutti i diritti riservati (All rights reserved) | Administrator |