title: Besides fibrillization: putative role of the peptide fragment 71-82 on the structural and assembly behavior of α-synuclein.
abstract: The fibrillization of α-synuclein (α-syn) is involved in Parkinson's disease, a neurodegenerative disorder that affects four million people in the world. The amino acid sequence 71-82 of this protein (VTGVTAVAQKTV) has appeared to be essential for fibril formation. In the present study, we have investigated the secondary structure and thermal stability of the peptide fragment 71-82, α-syn71-82, as a function of concentration and temperature, as well as its interactions with phospholipid model membranes using various spectroscopic techniques. The data show that α-syn71-82 is mainly disordered in solution with the presence of a few β-sheet structure elements. The peptide reversibly forms intermolecular β-sheets with increasing concentration and decreasing temperature, suggesting that it is subjected to a thermodynamic equilibrium between a monomeric and an oligomeric form. This equilibrium seems to be affected by the presence of zwitterionic membranes. Conversely, the influence of the peptide on zwitterionic lipid bilayers is small and concentration-dependent. By contrast, α-syn71-82 is strongly affected by anionic vesicles. The peptide indeed exhibits a dramatic conformational change, reflecting an extensive and irreversible self-aggregation, the majority of the amino acids being involved in a parallel β-sheet conformation. The aggregates appear to be located near the membrane surface but do not perturb significantly the membrane order. Comparing these results with the literature, it appears that α-syn71-82 shares several general properties and structural similarities with its parent protein. These common points suggest that the sequence 71-82 may overall contribute to the behavior and properties of α-syn.
authors.affiliation: Department of Chemistry, Regroupement Québécois de Recherche sur la Fonction, la Structure et l'Ingénierie des Protéines (PROTEO), Centre de Recherche sur les Matériaux Avancés (CERMA), Centre Québécois sur les Matériaux Fonctionnels (CQMF), Université Laval , Québec, Québec G1V 0A6, Canada.
authors.forename: Laurie
authors.initials: L
authors.lastname: Bédard
authors.forename: Thierry
authors.initials: T
authors.lastname: Lefèvre
authors.forename: Émilie
authors.initials: É
authors.lastname: Morin-Michaud
authors.forename: Michèle
authors.initials: M
authors.lastname: Auger
mesh_terms: D000682:Amyloid / Q000737:chemistry* / Q000378:metabolism; D002942:Circular Dichroism; D006801:Humans; D008051:Lipid Bilayers; D008958:Models, Molecular; D019906:Nuclear Magnetic Resonance, Biomolecular; D009994:Osmolar Concentration; D010446:Peptide Fragments / Q000737:chemistry* / Q000378:metabolism; D010713:Phosphatidylcholines / Q000737:chemistry / Q000378:metabolism; D010715:Phosphatidylglycerols / Q000737:chemistry / Q000378:metabolism; D066263:Protein Aggregation, Pathological; D011487:Protein Conformation; D054730:Protein Interaction Domains and Motifs; D055550:Protein Stability; D017433:Protein Structure, Secondary; D058767:Protein Unfolding; D012995:Solubility; D013696:Temperature; D051844:alpha-Synuclein / Q000737:chemistry* / Q000378:metabolism
chemical_list: D000682:Amyloid; D008051:Lipid Bilayers; D010446:Peptide Fragments; D010713:Phosphatidylcholines; D010715:Phosphatidylglycerols; C497604:SNCA protein, human; D051844:alpha-Synuclein; C000594017:alpha-synuclein (71-82), human; C060037:1-palmitoyl-2-oleoylglycero-3-phosphoglycerol; C028694:1-palmitoyl-2-oleoylphosphatidylcholine