A Generic Mechanism of Emergence of Amyloid Protofilaments from Disordered Oligomeric Aggregates 英文参考文献.docVIP
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A Generic Mechanism of Emergence of Amyloid Protofilaments from Disordered Oligomeric Aggregates 英文参考文献
AGenericMechanismofEmergenceofAmyloid
ProtofilamentsfromDisorderedOligomericAggregates
StefanAuer1*,FilipMeersman2,ChristopherM.Dobson3,MicheleVendruscolo3*
1CentreforSelfOrganisingMolecularSystems,UniversityofLeeds,Leeds,UnitedKingdom,2DepartmentofChemistry,KatholiekeUniversiteitLeuven,Leuven,Belgium,
3DepartmentofChemistry,UniversityofCambridge,Cambridge,UnitedKingdom
Abstract
The presence of oligomeric aggregates, which is often observed during the process of amyloid formation, has recently
attracted much attention because it has been associated with a range of neurodegenerative conditions including
Alzheimer’sandParkinson’sdiseases.Weprovideadescriptionofasequence-indepedentmechanismbywhichpolypeptide
chains aggregate by forming metastable oligomeric intermediate states prior to converting into fibrillar structures. Our
results illustrate that the formation of ordered arrays of hydrogen bonds drives the formation of b-sheets within the
disorderedoligomericaggregatesthatformearlyundertheeffectofhydrophobicforces.Individualb-sheetsinitiallyform
withrandomorientationsandsubsequentlytendtoalignintoprotofilamentsastheirlengthsincrease.Ourresultssuggest
thatamyloidaggregationrepresentsanexampleoftheOstwaldstepruleoffirst-orderphasetransitionsbyshowingthat
orderedcross-bstructuresemergepreferentiallyfromdisorderedcompactdynamicalintermediateassemblies.
Citation:AuerS,MeersmanF,DobsonCM,VendruscoloM(2008)AGenericMechanismofEmergenceofAmyloidProtofilamentsfromDisorderedOligomeric
Aggregates.PLoSComputBiol4(11):e1000222.doi:10.1371/journal.pcbi.1000222
Editor:RuthNussinov,NationalCancerInstituteUnitedStatesofAmericaandTelAvivUniversityIsrael
ReceivedMarch25,2008;AcceptedSeptember30,2008;PublishedNovember14,2008
Copyright: ? 2008 Auer et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits
unrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalauthorandsourcearecredited.
Funding:This
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