英文医学培训课件：Protein translation 02-20141124.pptx

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1、1968RobertW.Holley,HarBobindKhorana,MarshallW.Nirenberg“Fortheirinterpretationofthegeneticcodeanditsfunctioninproteinsynthesis”TheNobelPrizeinChemistry2009wasawardedjointlytoVenkatramanRamakrishnan,ThomasA.SteitzandAdaE.Yonath"forstudiesofthestructureandfunctionoftheribosome".PART1:ProteinSynthe

2、sisComponentsPART2:ProteinSynthesisProcessPART3:PosttranslationalProcessingandTargetingPART4:ProteinSynthesisinMedicinePART3:PosttranslationalProcessingandTargetingFromDNAtoprotein6FateofnascentpolypeptidesAssociationofnascentpolypeptidewithvariouschaperonesystemscommitsthemtofoldingpathwaysIfpr

3、oteinsfailtofold(onethirdofthenascentpolypeptides),theyarerecognizedandtargetedfordegradationThemacromoleculesassistingtheformationofproteinsecondarystructureincludeMolecularChaperonProteinDisulfideIsomerase(PDI)3.1ProteinFoldingNewlysynthesizedpolypeptidesmustformhigherorderstructurebeforetheyb

4、ecomefunctionalproteins8ProteinsareassistedinfoldingbymolecularchaperonesHeatshockproteins,Hsp60,Hsp70andHsp90arethreemainclassesHsp70recognizesexposed,unfoldedregionsofnewproteinchains-especiallyhydrophobicregionsItbindstotheseregions,protectingthemuntilproductivefoldingreactionscanoccur3.2.1Ch

5、aperonsMechanismhollowcylinderHsp60GroELformstwostacked7-memberedringsof60kDsubunits;GroESisadomeonthetopTheGroES-GroELComplex(Hsp60)11ModeloftheGroELcylinder(blue)inactionNascentproteinapparentlybindsreversiblymanytimestothewallsofthedonutstructure,eachtimedrivenbyATPhydrolysis,eventuallyadopti

6、ngitsfoldedstructure,thenbeingreleasedfromtheGroES-GroELcomplex12EucaryoticHsp90ChaperonesHsp90saccountfor1-2%oftotalcytosolicproteinSignaltransductionmoleculessuchastyrosinekinasereceptors,steroidhormonereceptors,non-receptortyrosinekinasesareclientsforHsp903.2.2Proteindisulfiteisomerasespatter

7、ndisulfidebondsCellularenvironmentisreducingCysteinesareoxidizedtoformS-SbondsIneukaryotes,proteindisulfideisomerase,PDI,usedforoxidationintheendoplasmicreticulum(ER)Thecorrectivedisulfideisveryimportantforthestructureofsecr