Effects of Molecular Crowding on the Dynamics of Intrinsically Disordered Proteins 英文参考文献.docVIP
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Effects of Molecular Crowding on the Dynamics of Intrinsically Disordered Proteins 英文参考文献
EffectsofMolecularCrowdingontheDynamicsof
IntrinsicallyDisorderedProteins
ElioA.Cino1,MikkoKarttunen2,Wing-YiuChoy1*
1DepartmentofBiochemistry,TheUniversityofWesternOntario,London,Ontario,Canada,2DepartmentofChemistry,UniversityofWaterloo,Waterloo,Ontario,Canada
Abstract
Inside cells, the concentration of macromolecules can reach up to 400g/L. In such crowded environments, proteins are
expectedtobehavedifferentlythaninvitro.Ithasbeenshownthatthestabilityandthefoldingrateofaglobularprotein
canbealteredbytheexcludedvolumeeffectproducedbyahighdensityofmacromolecules.However,macromolecular
crowdingeffectsonintrinsicallydisorderedproteins(IDPs)arelessexplored.Theseproteinscanbeextremelydynamicand
potentiallysampleawideensembleofconformationsundernon-denaturingconditions.ThedynamicpropertiesofIDPsare
intimatelyrelatedtothetimescaleofconformationalexchangewithintheensemble,whichgoverntargetrecognitionand
howtheseproteinsfunction.Inthiswork,weinvestigatedthemacromolecularcrowdingeffectsonthedynamicsofseveral
IDPs by measuring the NMR spin relaxation parameters of three disordered proteins (ProTa, TC1, and a-synuclein) with
different extents of residual structures. To aid the interpretation of experimental results, we also performed an MD
simulationofProTa.BasedontheMDanalysis,asimplemodeltocorrelatetheobservedchangesinrelaxationratestothe
alteration in protein motions under crowding conditions was proposed. Our results show that 1) IDPs remain at least
partiallydisordereddespitethepresenceofhighconcentrationofothermacromolecules,2)thecrowdedenvironmenthas
differentialeffectsontheconformationalpropensityofdistinctregionsofanIDP,whichmayleadtoselectivestabilization
ofcertaintarget-bindingmotifs,and3)thesegmentalmotionsofIDPsonthenanosecondtimescaleareretainedunder
crowded conditions. These findings strongly suggest that IDPs function as dynamic structural ensembles in cellular
environments.
Citation:CinoEA,KarttunenM,ChoyW-Y(2012)EffectsofMolecularCrowdingontheDynamicsofInt
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