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ChineseBulletinofLifeSciences18120062Vol.18,No.1Feb.,2006625014Q71AThefunctionandapplicationofmolecularchaperoneNIEZhong-Qing*,WUYong-Gang,MENGJian-Zhou(CollegeofAnimalScience&Technology,SichuanAgriculturalUniversity,Yaan625014,China)Abstract:Thispaperdiscussedtheclassification,function,mechanism,currentresearchprogressandtheapplicationprospectofthemolecularchaperone.Molecularchaperonesareaserialgroupofproteinswhicharefoundinalllivingorganism,helpingintheprocessofthefolding,assembly,transportationanddegradationofhugebiologicalmolecule,andparticipatinginantigenpresentation,inreplication,transcriptionandconforma-tionaldecisionofgeneticsubstance.Butmolecularchaperonesdont’tchangethemselvesatallwhentheywork.Withthefurtherdevelopmentofresearchandtheassociatedknowledgeofmolecularchaperone,therewillbeextensiveprospectsoftheapplicationinexploitingbio-products,improvingspecies,anti-aging,diagnosingandtreatingdisease,monitoringenvironmentandsoon.Keywords:molecularchaperone;proteinfolding;heatshockproteins;signaltransduction;apoptosis(molecularchaperone)(nucleoplasmin)Laskey1978(Xenopuslaevis)[1]Ellis[2][2](heatshockproteins,HSP)(folding)(assembly)1004-0374(2006)01-0084-062005-07-212005-10-08(1984)*(1983)(1983)11285HSPHSPHSP(celldifferentiation)2.1DnaK3040(Escherichiacoli)425min50Hsp70(immuno-fluorescencetechnique)Hsp70Hsp70[3]2.2()(1)[4]Levinthal[5]196810031005104710~13510341.610271(cumulativeselection)[5]NucleoplasminProteinXLNO-38NucleoplasminSHsp70Hsp70(Hsp40Hsp24)DnaK(DnaJGrpE)Ssa1-4SsB1SsC1SsD1BipHsc70grp78prp73Kar2pHsp60GroEL(GroES)cpn60(cpn10)RBPMif4pTCP-1TF55Tric(TCP-1)ThermosmeHsp90HtpGHsp90Hsp83Hsp87gp96Grp94Hsp100Hsp104ClpXSubtilisinprosequenceAlpha-lyticfactorprosequenceCaroxypeptidaseYprosequenceDsbC(DsbADsbG)PulSRNAStpAH-NSPDISscBTAPCalnexin(p88)CalreticulinERp57tapasinIiHLA-DMHLA-DO1/86(inclusionbody)Hsp70(bindingprotein,Bip)(signalsequence)BipATPATP[6]2.3Hsp70(precursorprotein)ATPHsp70(mHsp70)mHsp70mHsp70mHsp70mHsp70(2)[7](coatedvesicle)[8]2.4(nucleocapsid,NC)DNARNADNA[9]NCRNAcDNADNA(nuclearlocalizationprotein)(nuclearlocalizationsignal,NLS)DNADNA(nuclearpore)(nuclear)DNADNA[10](glucocoricoidreceptor,GR)Hsp90DNA(3)[11]2.5(nucleosome)(histone,H)DNA1Hsp70&Hsp60[4]2[7]3Hsp90[11]87DNADNADNA[12]2.6(cytoskeleton)CCT(thechaperonincontainingtaillesscomplexpolypeptide1)CCTCCTCCT--CCTATPATPCCT[13~14]2.7Hsp70HSC73Rb(retinoblastoma)Hsp40Rb(cellcycle)[15]Hsp90Hsp75(mitosis)(nuclearenvelope)RbRb[16]Hsp70[17]Hsp70JNK(JNKkinase)(apoptosis)Hsp70(stresssensor)JNKHsp70CAPAF-1(apoptosisproteaseactivatingfactor-1)ATPprocaspase-9Hsp70APAF-1APAF-1procaspase-9(apoptosome)[18]Hsp90Hsp90αNIH3T3[19]2.82.8.1MHC-(majorhistocompatibilitycomplex-I)HspTAP(ATP-dependenttransporterassociatedwithantigenprocessing)(calnexin)(calreticulin)ERp57tapasin(TAP-associatedgolycoprotein)Bip(GRP78)TAPTAPABC(ATP-bindingcassette)TAPMHC-IATPTAPMHC-IATPATPTAPMHC-ITAPβ2mTAPMHC-I[20]2.8.2MHC-II(majorhistocompatibilitycomplex-II)Ii(invariantchain)HLA-DMHLA-DOHLA-DMHLA-DM/pH(1)CLIP(class-II-associatedIipeptide)MHC-II((MHC-compartment,MIIC)HLA-DMMHC-II1/5pH=5.0HLA-DM3~12MHC-II(2)MHC-IIMIICpHHLA-DMMIICCLIPMHC-IIMHC-IIHLA-DMIiAPCCLIPHLA-DMMHC-IIHLA-DMIi(3)MHC-IIHLA-DMMHC-IIMHC-II88HLA-DMMHC-IIHLA-DMMHC-IIMHC-IICD4+T[20]2.9ShermanGoldberg[21]DnaK2.10Tower[22]Hsp70Hsp70FSV40TSV40TTP23Hsp90[23](WRN)[24]33.1CCT[25]CCTDNAHsp70GRP78GRP78[26]3.2Hsp70(immunodominantantigens)[27]BBHsp70[28]mRNAcDNAGCmRNA(6570)3.3DNA0.1~3.0um[29]89Teshima[30]DNA[31]ARNA3.43.5Hsp70Hsp70[32][1]LaskeyRA,HondaBM,MillsAD,etal.NucleosomesareassembledbyanacidicproteinwhichbindshistonesandtransfersthemtoDNA.Nature,1978,275:416~420[2]EllisJ.Proteinsasmolecularchaperones.Nature,1991,328(6129):378~379[3].[M].:,2003.476[4]AlbertsB,BrayD,LewisJ,etal.Molecularbiologyofthecell.3rded[M].NewYork:GarlandPub,Inc.,1994.215[5]LevinthalC.Aretherepathwaysforproteinfolding?JChemPhys,1968,65:44~45[6],,.[M].:,1998.125~132[7]KarpG.Cellandmolecularbiology:conceptsandexperiments.2nded[M].NewYork:JohnWiley&SonsInc.,1999.204[8],,.[M].:,2000.237~240[9]Lapadat-TapolskyM,DeRocquignyH,VanGentD,etal.InteractionsbetweenHIV-1nucleocapsidproteinandviralDNAmayhaveimportantfunctionsinthevirallifecycle.NucleicAcidsRes,1993,21(4):831~839[10].[M].:,2003.476~477[11]AlbertsB,BrayD,LewisJ,etal.Molecularbiologyofthecell.3rded[M].NewYork:GarlandPub,Inc.,1994.567[12].[M].:,2003.471~476[13]ValpuestaJM,Martin-BenitoJ,Gomez-PuertasP,etal.Structureandfunctionofaproteinfoldingmachine:theeukaryoticcytosolicchaperoninCCT.FEBSLett,2002,529(1):11~16[14]Martin-BenitoJ,BoskovicJ,Gomez-PuertasP,etal.Struc-tureofeukeryoticprefoldinandofitscomplexeswithunfoldedactinandthecytosolicchaperoninCCT.EMBOJ,2002,21(23):6377~6386[15]Blond-ElguindiS,CwirlaSE,DowerWJ,etal.Affinitypanningofalibraryofpeptidesdisplayedonbacterioph-agesrevealsthebindingspecificityofBiP.Cell,1993,75(4):717~728[16]ChenCF,ChenY,DaiK,etal.AnewmemberoftheHsp90familyofmolecularchaperonesinteractswiththeretino-blastomaproteinduringmitosisandheatshock.MolCellBiol,1996,16(9):4691~4699[1