高级细胞生物学-1ppt课件

.,1,高级细胞生物学（35学时）,吉林大学生命科学学院金英花,.,2,教学大纲,第一章细胞周期及其调控第一节蛋白质的基本特征第二节细胞周期第三节Cyclin家族、Cdk家族第四节CDK活性的调控机制第二章细胞增殖周期中信号转导第一节CDK的重要底物及其作用第二节生长因子信号与细胞周期运行第三节细胞周期阻滞信号的启动与信号转导第四节细胞周期的研究方法,.,3,第三章细胞凋亡及其调控第一节细胞凋亡第二节Caspase家族及其激活途径第三节Bcl-2家族、IAP家族及其对细胞凋亡的调控第四章细胞凋亡过程中的信号转导第一节Caspase的底物第二节细胞凋亡的调控第三节细胞凋亡的研究方法,.,4,第五章p53与细胞周期、细胞凋亡第一节p53的结构特征与亚细胞定位第二节p53对细胞周期周期的调控第三节p53对细胞周期凋亡的调控第六章细胞自噬第一节细胞自噬第二节细胞自噬的分子机制第三节细胞自噬与抗衰老第四节答疑与讨论,.,5,教材1）MolecularBiologyofTHECELL(BruceAlbertsetc.),FifthEdition(2007)2）癌生物学（TheBiologyofCancer),RAWeinberg著，詹启敏等译（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,形成蛋白质的20种氨基酸,.,10,.,11,.,12,ThreeTypesofNoncovalentBondsinProteins,.,13,*Secretedorcell-surfaceproteinsoftenformdisulfidebondsbetweenthetwo-SHgroupsofcytosineresidues(Ex:Lysozyme):;*Disulfidebondsdonotchangetheconformationofaproteinbutactasatomicstaplestoreinforceitsmostfavoredconformation.,.,14,Stericlimitationonthebondanglesinpolypeptidechain,.,15,RamachandranPlot(拉马钱德兰图),Thereweretensofthousandsofhigh-resolutionproteinstructuresdeterminedbyX-raycrystallographyanddepositedintheProteinDataBank(PDB).Fromonethousanddifferentproteinchains,Ramachandranplotsofover200,000aminoacidswereplotted,showingsomesignificantdifferences,especiallyforglycine(Hovmlleretal2002).,AAlocatedina-helix,.,16,Mostpolypeptidechains,foldintoonlyoneparticularconformations;2)Mostproteinscanfoldspontaneouslyintotheircorrectshape;3)Theshapeofaproteinmoleculeisdeterminedbyitsaminoacidsequence.,要点I,.,17,Backbone,Ribbon,.,18,Wire,Space-filling,.,19,ProteinshaveDifferentLevelofStructuralOrganization,蛋白质构象（conformation）：形成蛋白质的每个原子在空间的特异排列；Primarystructure:氨基酸之间形成的所有共价键包括二硫键的位置，由形成蛋白质的氨基酸序列决定的。Secondarystructure:多肽链中由相邻氨基酸残基间形成的有规律的、反复出现的空间排列；Tertiarystructure:多肽链的完整三维结构，形成多肽链的所有氨基酸的空间分布；Quaternarystructure:多个多肽链组成的蛋白质中，各个亚基之间空间关系。,.,20,ProteinshaveDifferentLevelofStructuralOrganization,.,21,CAP(cataboliteactivatorprotein),Domain：蛋白质中具有特异结构与独立功能的区域，40-350氨基酸组成。,.,22,1）Onlyaverysmallfractionofpossibleproteinswouldadoptastablethree-dimensionalconformation;2）Proteinswithoutstableconformationwouldnotbeusefulandbeeliminatedbynaturalselection;3）Proteinswithextremelystableconformationhastheprecisechemicalpropertiesthatenabletheproteintoperformaspecificcatalyticorstructuralfunctioninthecell;,要点II,.,23,Immunoglobinlightchain,Cytochromeb562,NAD-bindingdomainoflacticdehydrogenase,Three-dimensionalstructureofseveraldifferentlyorganizedproteindomains,.,24,（弹性蛋白酶）,（胰凝乳蛋白酶）,Comparisonoftheconformationsofthetwoserineproteases,.,25,Newproteinsusuallyevolvebyalterationsofoldone,1）Onceaproteinwithusefulsurfacepropertieshasevolved,itsbasicstructurecanbeincorporatedinmanyotherproteins；2)Proteinsofdifferentbutrelatedfunctioninpresent-dayorganismsoftenhavesimilaraminoacidsequences；3)Suchfamiliesofproteinsarebelievedtohaveevolvedfromasingleancestralgenethatduplicatedinthecourseofevolutiontogiverisetoothergenesinwhichmutationsgraduallyaccumulatedtoproducerelatedproteinswithnewfunctions.,要点III,.,26,.,27,Newproteincanevolvebyrecombiningpreexistingpolypetidedomain,Newsurfacescanbegeneratedbyjoiningtwoormoreproteintogetherbynoncovalentinteractionbetweenthem.Thiscombiningofproteinstomakelargerfunctionalproteinassembliesiscommon;Analternativewa