title: Exploring the mechanism of formation of native-like and precursor amyloid oligomers for the native acylphosphatase from Sulfolobus solfataricus.
abstract: Over 40 human diseases are associated with the formation of well-defined proteinaceous fibrillar aggregates. Since the oligomers precursors to the fibrils are increasingly recognized to be the causative agents of such diseases, it is important to elucidate the mechanism of formation of these early species. The acylphosphatase from Sulfolobus solfataricus is an ideal system as it was found to form, under conditions in which it is initially native, two types of prefibrillar aggregates: (1) initial enzymatically active aggregates and (2) oligomers with characteristics reminiscent of amyloid protofibrils, with the latter originating from the structural reorganization of the initial assemblies. By studying a number of protein variants with a variety of biophysical techniques, we have identified the regions of the sequence and the driving forces that promote the first aggregation phase and show that the second phase consists in a cooperative conversion involving the entire globular fold.
authors.affiliation: Dipartimento di Scienze Biochimiche, Università di Firenze, Viale Morgagni 50, 50134 Firenze, Italy.
authors.forename: Georgia
authors.initials: G
authors.lastname: Plakoutsi
authors.forename: Francesco
authors.initials: F
authors.lastname: Bemporad
authors.forename: Maria
authors.initials: M
authors.lastname: Monti
authors.forename: Daniela
authors.initials: D
authors.lastname: Pagnozzi
authors.forename: Piero
authors.initials: P
authors.lastname: Pucci
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Chiti
mesh_terms: D017766:Acid Anhydride Hydrolases / Q000737:chemistry*; D000595:Amino Acid Sequence; D000682:Amyloid / Q000737:chemistry*; D008958:Models, Molecular; D008969:Molecular Sequence Data; D011487:Protein Conformation; D017510:Protein Folding; D048229:Sulfolobus solfataricus / Q000201:enzymology*; D000097024:Acylphosphatase
chemical_list: D017766:Acid Anhydride Hydrolases; D000682:Amyloid; D000097024:Acylphosphatase