title: Trehalose-Induced Structural Transition Accelerates Aggregation of α-Synuclein.
abstract: Fibrillation of α-synuclein proceeds through distinct stages, with oligomers combining to form the seed or the nucleus, followed by exponential and saturation phases. Osmolytes are considered to act as protein stabilizers by virtue of their ability to inhibit protein aggregation. Trehalose, a non-reducing disaccharide which is conventionally used as a stabilizer, was found to order α-synuclein, a natively disordered protein, into a non-native conformation such that the protein folding pathway is driven towards aggregation. Thus, by ordering the pathway intermediates, the osmolyte trehalose exerts variable effect on an intrinsically disordered protein when compared with its effect on natively folded proteins.
authors.affiliation: Department of Biotechnology, National Institute of Pharmaceutical Education and Research, Sector 67, S.A.S. Nagar, Punjab, 160062, India.
authors.forename: Vishal
authors.initials: V
authors.lastname: Naik
authors.affiliation: Department of Biotechnology, National Institute of Pharmaceutical Education and Research, Sector 67, S.A.S. Nagar, Punjab, 160062, India.
authors.forename: Jay
authors.initials: J
authors.lastname: Kardani
authors.affiliation: Department of Biotechnology, National Institute of Pharmaceutical Education and Research, Sector 67, S.A.S. Nagar, Punjab, 160062, India. ipsita@niper.ac.in.
authors.forename: Ipsita
authors.initials: I
authors.lastname: Roy
mesh_terms: D006801:Humans; D064267:Intrinsically Disordered Proteins / Q000737:chemistry; D011487:Protein Conformation; D017510:Protein Folding; D014199:Trehalose / Q000737:chemistry*; D051844:alpha-Synuclein / Q000737:chemistry*
chemical_list: D064267:Intrinsically Disordered Proteins; D051844:alpha-Synuclein; D014199:Trehalose
keywords: Fibrillation; Intrinsically disordered proteins; Nucleation; Oligomers; Protease sensitivity