生理化學教學課件：ch3 Nucleotide

NucleotideChapter3WuXZ,PhDBiochemistryShanghaiMedicalCollegeXz_wu@542376972Degreesoffreedom:5’3’WuXZ,PhDXz_wu@542376973StructuralVariationDefinedbyBasesnormalfrequentneverNever(exceptinintercalation)CommonCommonWuXZ,PhDBiochemistryShanghaiMedicalCollegeXz_wu@542376974PropellerTwistBuckleTextbookRealLife3.6nmWuXZ,PhDXz_wu@542376975Pyrimidine-PurineStepsHaveLittleBaseStacking5’3’3’5’CGATWuXZ,PhDXz_wu@542376976Purine-PyrimidineStepsHaveExtensiveBaseStacking5’3’3’CATG5’WuXZ,PhDXz_wu@542376977DoublehelixAlowhumidityMorecompactRNA-DNARNA-RNA11base/turntilted75%Left-handedzigzagPu-PyIncellsDNAZDNAZWuXZ,PhDXz_wu@542376978WuXZ,PhDXz_wu@542376979RotationofGlycosidicBondN3A,BDNAZDNA(Gonly)ATransCisWuXZ,PhDXz_wu@5423769710ABZHandednessPitchBaseInclinationWuXZ,PhDXz_wu@5423769711typeABZHelixpatternRight-handedRight-handedLeft-handeddiameter26A20A18ABasepairperturn1110.512AnglebetweenBases33o34.2o-60ohumidity75%92%GlycosidicbondtranstranstranscisDoublehelicesWuXZ,PhDXz_wu@5423769712(四)OtherstructuresCandTinonestrandandAandGintheother.

Atriple-strandedDNAstructurepoly(A)andpolydeoxy(U)aremixedcanbetargetedbyshortmatchingpoly(C+T).1.HoogsteenbasepairsWuXZ,PhDXz_wu@5423769713Hoogsteenbasepairs

WuXZ,PhDBiochemistryShanghaiMedicalCollegeXz_wu@5423769714WuXZ,PhDBiochemistryShanghaiMedicalCollegeXz_wu@5423769715H-DNAnatural(recombinationandDNArepair).WuXZ,PhDXz_wu@54237697162.QuadruplehelixesofDNAWuXZ,PhDXz_wu@5423769717ParalleltelomerequadrupleWuXZ,PhDBiochemistryShanghaiMedicalCollegeXz_wu@5423769718

堿基序列依賴性的局部DNA可形成發(fā)夾形或十字形結(jié)構(gòu)3.LocalhairpinorcrossstructureWuXZ,PhDXz_wu@5423769719二、

TertiarystructureofDNA

thedoublestrandsareintertwined

fold,twist,andturnfurther

superhelixorsupercoilWuXZ,PhDXz_wu@54237697201Lengthoflinearmolecule.Significance2Diameterofacell3SupercoilingreducesthesizeofDNAforpackage.WuXZ,PhDBiochemistryShanghaiMedicalCollegeXz_wu@5423769721TwistInducesSupercoilingWuXZ,PhDXz_wu@5423769722(一)topoisomers1.DNAtopoisomerdifferentin

writhedirectionLocal,entireTwistWuXZ,PhDXz_wu@5423769723Positivesupercoilwoundaroundoneanothermoretightly

TwistinginthesamesenseWuXZ,PhDBiochemistryShanghaiMedicalCollegeXz_wu@5423769724Negativesupercoil

TwistingintheoppositesenselesstightlyWuXZ,PhDXz_wu@5423769725

(二)ManyDNAMoleculesAreCircular.mitochondriaDNAprokaryoticgenomicDNAsviralDNAschloroplastsunicellulareukaryotesCircularDNAWuXZ,PhDXz_wu@54237697261.CircularDNAforms

aclosedstructure.

nofreeends

cannotunwindfreelyWuXZ,PhDXz_wu@5423769727UnwindingandsubsequentsupercoilingnucleoidsWuXZ,PhDXz_wu@54237697282.Twist&WritheThetwististhenumberofhelicalturnsintheDNAWritheisglobalcontortionsofaDNAmolecule.interconvertibleWuXZ,PhDXz_wu@5423769729Sumoftwistandwrithe.Lk=Tw+WrWuXZ,PhDXz_wu@5423769730BeltanalogtoSupercoiling.

WuXZ,PhDXz_wu@5423769731LK↓negativesupercoilingand/orunderwinding↑LK↑negativesupercoiling↓/underwinding↓.leftrightΔLk,theChangeof

LKWuXZ,PhDXz_wu@5423769732LKOnlyifbreaks,willLKchange..aninvariantpropertyofDNA

cannotchangefreelyWuXZ,PhDXz_wu@54237697333.TopoisomerasetypeImakeatransientbreakinonestrandofDNA(Ⅰ&Ⅲ)Releasenegativesupercoilschangelinkingnumber+1peractionWuXZ,PhDBiochemistryShanghaiMedicalCollegeXz_wu@5423769734topoisomeraseI

noATPWuXZ,PhDBiochemistryShanghaiMedicalCollegeXz_wu@5423769735TypeIItopoisomerasesATPWuXZ,PhDXz_wu@5423769736（三）EukaryoticNuclearDNAFormsChromatin.

1DNA+proteins→chromatin2ChromatinismadeofnucleosomeWuXZ,PhDXz_wu@5423769737CoreparticlesLinkingDNAHistonecoreWuXZ,PhDXz_wu@5423769738

Solenoidmodelofthe30-nmcondensedchromatinfiberinasideview.

[AdaptedfromM.Grunstein,1992,Sci.Am.

267:68]WuXZ,PhDXz_wu@54237697396nucleosomes/turn10nmSolenoidChromosome1400nm10000x300nmfiber,40x700nmfiberDiameter30nm100xWuXZ,PhDXz_wu@5423769740（四）telomerenaturalendtheterminusofchromosomalDNA+relatedproteinIt"seals"theendWuXZ,PhDXz_wu@5423769741TelomerestructureWuXZ,PhDBiochemistryShanghaiMedicalCollegeXz_wu@5423769742TelomeraseWuXZ,PhDXz_wu@5423769743三、DNA

asthegeneticmaterialWuXZ,PhDBiochemistryShanghaiMedicalCollegeXz_wu@5423769744(一)BacterialDNAtransformationWuXZ,PhDXz_wu@5423769745(二)genomeandgenegeneGenome:wholegeneticinformationgenegeneWuXZ,PhDBiochemistryShanghaiMedicalCollegeXz_wu@5423769746SizeofDNAmolecule

MWBase(kb)ChromosomeGeneMicroorganismSV40virus3x1065λphage3.4x10750Ecoli2.2x109460014405mammalianmice1.5x1012250萬403-3.5萬

Homosapiens1.8x1012320萬463-3.5萬WuXZ,PhDBiochemistryShanghaiMedicalCollegeXz_wu@5423769747mRNAhnRNArRNAtRNASmallRNA第三節(jié)StructureandFunctionofRNAWuXZ,PhDXz_wu@5423769748(一)eukaryoticmRNAiscapped

mRNAiscappedlinkagemethylgroups5’terminusguanine一、EukaryoticmRNAWuXZ,PhDBiochemistryShanghaiMedicalCollegeXz_wu@54237697491、Capsequencem7GpppNm-WuXZ,PhDBiochemistryShanghaiMedicalCollegeXz_wu@5423769750WuXZ,PhDXz_wu@5423769751NpApppCapisaddedaftertranscription.5′+↓5`5`

GppppppGPPpWuXZ,PhDBiochemistryShanghaiMedicalCollegeXz_wu@5423769752MethylationWuXZ,PhDBiochemistryShanghaiMedicalCollegeXz_wu@5423769753EveryeukaryoticmRNAiscapped.morethanonetype?

WhethermRNAisinvariant?

Theproportions.WuXZ,PhDBiochemistryShanghaiMedicalCollegeXz_wu@5423769754RolesofCapCapofmRNAprotectiontranslationCapbindingproteintransplantationWuXZ,PhDBiochemistryShanghaiMedicalCollegeXz_wu@54237697552、mRNAshave3’PolyAtailmostmammalianmRNAspolyadenylatedwith20-250AWuXZ,PhDXz_wu@5423769756SynthesisofpolyAtailpoly(A)polymerase20-250enzymeaddingsite

free3′-OHendWuXZ,PhDBiochemistryShanghaiMedicalCollegeXz_wu@5423769757BindingofproteinsOnePABP~70kDinevery10-20A.astretchofpoly(A)toalargemassofprotein.PABPPABP