Multi-Scale Simulations Provide Supporting Evidence for the Hypothesis of Intramolecular Protein Translocation in GroELGroES Complexes 英文参考文献.docVIP

Multi-Scale Simulations Provide Supporting Evidence for the Hypothesis of Intramolecular Protein Translocation in GroELGroES Complexes 英文参考文献.doc

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Multi-Scale Simulations Provide Supporting Evidence for the Hypothesis of Intramolecular Protein Translocation in GroELGroES Complexes 英文参考文献

Multi-ScaleSimulationsProvideSupportingEvidencefor theHypothesisofIntramolecularProteinTranslocation inGroEL/GroESComplexes IvanColuzza1*,AlfonsoDeSimone1,FrancaFraternali2,DaanFrenkel1,3 1DepartmentofChemistry,UniversityofCambridge,Cambridge,UnitedKingdom,2RandallDivisionofCellandMolecularBiophysics,King’sCollegeLondon,London, UnitedKingdom,3FOMInstituteAMOLF,Amsterdam,TheNetherlands Abstract Thebiologicalfunctionofchaperonecomplexesistoassistthefoldingofnon-nativeproteins.ThewidelystudiedGroEL chaperoninisadouble-barreledcomplexthatcantrapnon-nativeproteinsinoneofitstwobarrels.TheATP-drivenbinding of a GroES cap then results in a major structural change of the chamber where the substrate is trapped and initiates a refoldingattempt.Thetwobarrelsoperateanti-synchronously.Thecentralregionbetweenthetwobarrelscontainsahigh concentrationofdisorderedproteinchains,theroleofwhichwasthusfarunclear.Inthisworkwereportacombinationof atomisticandcoarse-grainedsimulationsthatprobethestructureanddynamicsoftheequatorialregionoftheGroEL/GroES chaperonincomplex.Surprisingly,oursimulationsshowthattheequatorialregionprovidesatranslocationchannelthatwill blockthepassageoffoldedproteinsbutallowsthepassageofsecondaryunitswiththediameterofanalpha-helix.We computethefree-energybarrierthathastobeovercomeduringtranslocationandfindthatitcaneasilybecrossedunder theinfluenceofthermalfluctuations.Hence,stronglynon-nativeproteinscanbesqueezedliketoothpastefromonebarrel tothenextwheretheywillrefold.Proteinsthatarealreadyfairlyclosetothenativestatewillnottranslocatebutcanrefold inthechamberwheretheyweretrapped.Severalexperimentalresultsarecompatiblewiththisscenario,andinthecaseof the experiments of Martin and Hartl, intra chaperonin translocation could explain why under physiological crowding conditionsthechaperonindoesnotreleasethesubstrateprotein. Citation:ColuzzaI,DeSimoneA,FraternaliF,FrenkelD(2008)Multi-ScaleSimulationsProvideSupportingEvidencefortheHypothesisofIntramolecularProtein Transloc

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