.,1,高級(jí)細(xì)胞生物學(xué)（35學(xué)時(shí)）,吉林大學(xué)生命科學(xué)學(xué)院金英花,.,2,教學(xué)大綱,第一章細(xì)胞周期及其調(diào)控第一節(jié)蛋白質(zhì)的基本特征第二節(jié)細(xì)胞周期第三節(jié)Cyclin家族、Cdk家族第四節(jié)CDK活性的調(diào)控機(jī)制第二章細(xì)胞增殖周期中信號(hào)轉(zhuǎn)導(dǎo)第一節(jié)CDK的重要底物及其作用第二節(jié)生長(zhǎng)因子信號(hào)與細(xì)胞周期運(yùn)行第三節(jié)細(xì)胞周期阻滯信號(hào)的啟動(dòng)與信號(hào)轉(zhuǎn)導(dǎo)第四節(jié)細(xì)胞周期的研究方法,.,3,第三章細(xì)胞凋亡及其調(diào)控第一節(jié)細(xì)胞凋亡第二節(jié)Caspase家族及其激活途徑第三節(jié)Bcl-2家族、IAP家族及其對(duì)細(xì)胞凋亡的調(diào)控第四章細(xì)胞凋亡過(guò)程中的信號(hào)轉(zhuǎn)導(dǎo)第一節(jié)Caspase的底物第二節(jié)細(xì)胞凋亡的調(diào)控第三節(jié)細(xì)胞凋亡的研究方法,.,4,第五章p53與細(xì)胞周期、細(xì)胞凋亡第一節(jié)p53的結(jié)構(gòu)特征與亞細(xì)胞定位第二節(jié)p53對(duì)細(xì)胞周期周期的調(diào)控第三節(jié)p53對(duì)細(xì)胞周期凋亡的調(diào)控第六章細(xì)胞自噬第一節(jié)細(xì)胞自噬第二節(jié)細(xì)胞自噬的分子機(jī)制第三節(jié)細(xì)胞自噬與抗衰老第四節(jié)答疑與討論,.,5,教材1）MolecularBiologyofTHECELL(BruceAlbertsetc.),FifthEdition(2007)2）癌生物學(xué)（TheBiologyofCancer),RAWeinberg著，詹啟敏等譯（2009年版）,.,6,.,7,ApproximateChemicalCompositionofaTypicalBacteriumandATypicalMammalianCell,PercentofTotalcellweight,E.Coli,MammalianCell,Component,H2O7070Inorganicions(Na+,K+,Mg2+,Ca2+,Cl-)11Miscellaneoussmallmetabolites33Proteins1518RNA61.1DNA10.25Phospholipids23OtherLipids-2Polysaccharides22Cellvolume210-12cm3410-9cm3Relativecellvolume12000,.,8,Proteins,1)Cellsbuildingblocks;2)Executenearlyallthecellsfunction;3)Formchannelsandpumps;4)Carriesmessagefromonecelltoanother;5)Actassignalintegrators;6)Serveastinymolecularmachineswithmovingparts:kinesin,topoisomerase;6)Antibody,toxin,hormones,antifreezemolecules,elasticfibers；7)Sourceofluminescence,.,9,形成蛋白質(zhì)的20種氨基酸,.,10,.,11,.,12,ThreeTypesofNoncovalentBondsinProteins,.,13,*Secretedorcell-surfaceproteinsoftenformdisulfidebondsbetweenthetwo-SHgroupsofcytosineresidues(Ex:Lysozyme):;*Disulfidebondsdonotchangetheconformationofaproteinbutactasatomicstaplestoreinforceitsmostfavoredconformation.,.,14,Stericlimitationonthebondanglesinpolypeptidechain,.,15,RamachandranPlot(拉馬錢(qián)德蘭圖),Thereweretensofthousandsofhigh-resolutionproteinstructuresdeterminedbyX-raycrystallographyanddepositedintheProteinDataBank(PDB).Fromonethousanddifferentproteinchains,Ramachandranplotsofover200,000aminoacidswereplotted,showingsomesignificantdifferences,especiallyforglycine(Hovmlleretal2002).,AAlocatedina-helix,.,16,Mostpolypeptidechains,foldintoonlyoneparticularconformations;2)Mostproteinscanfoldspontaneouslyintotheircorrectshape;3)Theshapeofaproteinmoleculeisdeterminedbyitsaminoacidsequence.,要點(diǎn)I,.,17,Backbone,Ribbon,.,18,Wire,Space-filling,.,19,ProteinshaveDifferentLevelofStructuralOrganization,蛋白質(zhì)構(gòu)象（conformation）：形成蛋白質(zhì)的每個(gè)原子在空間的特異排列；Primarystructure:氨基酸之間形成的所有共價(jià)鍵包括二硫鍵的位置，由形成蛋白質(zhì)的氨基酸序列決定的。Secondarystructure:多肽鏈中由相鄰氨基酸殘基間形成的有規(guī)律的、反復(fù)出現(xiàn)的空間排列；Tertiarystructure:多肽鏈的完整三維結(jié)構(gòu)，形成多肽鏈的所有氨基酸的空間分布；Quaternarystructure:多個(gè)多肽鏈組成的蛋白質(zhì)中，各個(gè)亞基之間空間關(guān)系。,.,20,ProteinshaveDifferentLevelofStructuralOrganization,.,21,CAP(cataboliteactivatorprotein),Domain：蛋白質(zhì)中具有特異結(jié)構(gòu)與獨(dú)立功能的區(qū)域，40-350氨基酸組成。,.,22,1）Onlyaverysmallfractionofpossibleproteinswouldadoptastablethree-dimensionalconformation;2）Proteinswithoutstableconformationwouldnotbeusefulandbeeliminatedbynaturalselection;3）Proteinswithextremelystableconformationhastheprecisechemicalpropertiesthatenabletheproteintoperformaspecificcatalyticorstructuralfunctioninthecell;,要點(diǎn)II,.,23,Immunoglobinlightchain,Cytochromeb562,NAD-bindingdomainoflacticdehydrogenase,Three-dimensionalstructureofseveraldifferentlyorganizedproteindomains,.,24,（彈性蛋白酶）,（胰凝乳蛋白酶）,Comparisonoftheconformationsofthetwoserineproteases,.,25,Newproteinsusuallyevolvebyalterationsofoldone,1）Onceaproteinwithusefulsurfacepropertieshasevolved,itsbasicstructurecanbeincorporatedinmanyotherproteins；2)Proteinsofdifferentbutrelatedfunctioninpresent-dayorganismsoftenhavesimilaraminoacidsequences；3)Suchfamiliesofproteinsarebelievedtohaveevolvedfromasingleancestralgenethatduplicatedinthecourseofevolutiontogiverisetoothergenesinwhichmutationsgraduallyaccumulatedtoproducerelatedproteinswithnewfunctions.,要點(diǎn)III,.,26,.,27,Newproteincanevolvebyrecombiningpreexistingpolypetidedomain,Newsurfacescanbegeneratedbyjoiningtwoormoreproteintogetherbynoncovalentinteractionbetweenthem.Thiscombiningofproteinstomakelargerfunctionalproteinassembliesiscommon;Analternativewa