title: Granular assembly of alpha-synuclein leading to the accelerated amyloid fibril formation with shear stress.
abstract: alpha-Synuclein participates in the Lewy body formation of Parkinson's disease. Elucidation of the underlying molecular mechanism of the amyloid fibril formation is crucial not only to develop a controlling strategy toward the disease, but also to apply the protein fibrils for future biotechnology. Discernable homogeneous granules of alpha-synuclein composed of approximately 11 monomers in average were isolated in the middle of a lag phase during the in vitro fibrillation process. They were demonstrated to experience almost instantaneous fibrillation during a single 12-min centrifugal membrane-filtration at 14,000 x g. The granular assembly leading to the drastically accelerated fibril formation was demonstrated to be a result of the physical influence of shear force imposed on the preformed granular structures by either centrifugal filtration or rheometer. Structural rearrangement of the preformed oligomomeric structures is attributable for the suprastructure formation in which the granules act as a growing unit for the fibril formation. To parallel the prevailing notion of nucleation-dependent amyloidosis, we propose a double-concerted fibrillation model as one of the mechanisms to explain the in vitro fibrillation of alpha-synuclein, in which two consecutive concerted associations of monomers and subsequent oligomeric granular species are responsible for the eventual amyloid fibril formation.
authors.affiliation: School of Chemical and Biological Engineering, College of Engineering, Seoul National University, Gwanak-Ku, Seoul, Korea.
authors.forename: Ghibom
authors.initials: G
authors.lastname: Bhak
authors.forename: Jung-Ho
authors.initials: JH
authors.lastname: Lee
authors.forename: Ji-Sook
authors.initials: JS
authors.lastname: Hahn
authors.forename: Seung R
authors.initials: SR
authors.lastname: Paik
mesh_terms: D000682:Amyloid / Q000737:chemistry*; D002498:Centrifugation; D016631:Lewy Bodies / Q000378:metabolism; D010300:Parkinson Disease / Q000378:metabolism; D012212:Rheology; D051844:alpha-Synuclein / Q000737:chemistry*
chemical_list: D000682:Amyloid; D051844:alpha-Synuclein