Granular Assembly of α-Synuclein Leading to the Accelerated Amyloid Fibril Formation with Shear Stress 英文参考文献.docVIP
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Granular Assembly of α-Synuclein Leading to the Accelerated Amyloid Fibril Formation with Shear Stress 英文参考文献
GranularAssemblyofa-SynucleinLeadingtothe
AcceleratedAmyloidFibrilFormationwithShearStress
GhibomBhak,Jung-HoLee,Ji-SookHahn,SeungR.Paik*
SchoolofChemicalandBiologicalEngineering,CollegeofEngineering,SeoulNationalUniversity,Gwanak-Ku,Seoul,Korea
Abstract
a-Synuclein participates in the Lewy body formation of Parkinson’s disease. Elucidation of the underlying molecular
mechanismoftheamyloidfibrilformationiscrucialnotonlytodevelopacontrollingstrategytowardthedisease,butalso
to apply the protein fibrils for future biotechnology. Discernable homogeneous granules of a-synuclein composed of
approximately11monomersinaveragewereisolatedinthemiddleofalagphaseduringtheinvitrofibrillationprocess.
They were demonstrated to experience almost instantaneous fibrillation during a single 12-min centrifugal membrane-
filtrationat14,0006g.Thegranularassemblyleadingtothedrasticallyacceleratedfibrilformationwasdemonstratedtobe
aresultofthephysicalinfluenceofshearforceimposedonthepreformedgranularstructuresbyeithercentrifugalfiltration
or rheometer. Structural rearrangement of the preformed oligomomeric structures is attributable for the suprastructure
formationinwhichthegranulesactasagrowingunitforthefibrilformation.Toparalleltheprevailingnotionofnucleation-
dependentamyloidosis,weproposeadouble-concertedfibrillationmodelasoneofthemechanismstoexplaintheinvitro
fibrillation of a-synuclein, in which two consecutive concerted associations of monomers and subsequent oligomeric
granularspeciesareresponsiblefortheeventualamyloidfibrilformation.
Citation:BhakG,LeeJ-H,HahnJ-S,PaikSR(2009)GranularAssemblyofa-SynucleinLeadingtotheAcceleratedAmyloidFibrilFormationwithShearStress.PLoS
ONE4(1):e4177.doi:10.1371/journal.pone.0004177
Editor:HilalLashuel,SwissFederalInstituteofTechnologyLausanne,Switzerland
ReceivedSeptember12,2008;AcceptedDecember4,2008;PublishedJanuary12,2009
Copyright: ? 2009 Bhak et al. This is an open-access article distributed under the terms of the Creative Commons Attribution L
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