title: Fibrillation mechanism of a model intrinsically disordered protein revealed by 2D correlation deep UV resonance Raman spectroscopy.
abstract: Understanding of numerous biological functions of intrinsically disordered proteins (IDPs) is of significant interest to modern life science research. A large variety of serious debilitating diseases are associated with the malfunction of IDPs including neurodegenerative disorders and systemic amyloidosis. Here we report on the molecular mechanism of amyloid fibrillation of a model IDP (YE8) using 2D correlation deep UV resonance Raman spectroscopy. YE8 is a genetically engineered polypeptide, which is completely unordered at neutral pH yet exhibits all properties of a fibrillogenic protein at low pH. The very first step of the fibrillation process involves structural rearrangements of YE8 at the global structure level without the detectable appearance of secondary structural elements. The formation of β-sheet species follows the global structural changes and proceeds via the simultaneous formation of turns and β-strands. The kinetic mechanism revealed is an important new contribution to understanding of the general fibrillation mechanism proposed for IDP.
authors.affiliation: Department of Chemistry, University at Albany, SUNY, 1400 Washington Avenue, Albany, New York 12222, USA.
authors.forename: Vitali
authors.initials: V
authors.lastname: Sikirzhytski
authors.forename: Natalya I
authors.initials: NI
authors.lastname: Topilina
authors.forename: Gaius A
authors.initials: GA
authors.lastname: Takor
authors.forename: Seiichiro
authors.initials: S
authors.lastname: Higashiya
authors.forename: John T
authors.initials: JT
authors.lastname: Welch
authors.forename: Vladimir N
authors.initials: VN
authors.lastname: Uversky
authors.forename: Igor K
authors.initials: IK
authors.lastname: Lednev
mesh_terms: D000682:Amyloid / Q000737:chemistry*; D008958:Models, Molecular; D013059:Spectrum Analysis, Raman; D014466:Ultraviolet Rays
chemical_list: D000682:Amyloid