第13章 核酸的结构

第十三章核酸的结构StructureofNucleicAcid核酸的化学组成：核苷酸（nucleotide）

核酸（nucleicacid）磷酸（phosphoricacid）核苷（nucleoside）戊糖（pentose）碱基（base）↓核酸

核糖核苷酸（ribonucleotide）脱氧核糖核酸（DNA）

脱氧核糖核苷酸（deoxyribonucleotide）核糖核酸（RNA）Thenucleicacids(DNAandRNA)arepolymersofnucleotideunitsDNAconsistsoffourkindsofdeoxyribonucleotideunitslinkedtogetherthroughcovalentbonds.Eachnucleotideunitismadeofanitrogenousbase(thevariouspartinthefourdifferentdeoxyribonucleotides),apentosesugar,andaphosphategroup.Thenitrogenousbasecanbeadenine(A),guanine(G),cytosine(C),orthymine(T).Thenitrogenousbasesarederivatives衍生物oftwoparentcompounds,pyrimidineandpurine.Thecarbonandnitrogenatomsinthepyrimidineandpurineringsarenumbered.H两类核酸的基本化学组成RNADNA组成戊糖核糖（D-ribose）脱氧核糖（D-2-deoxyribose）碱基腺嘌呤（adenine）、鸟嘌呤（guanine）、胞嘧啶（cytosine）尿嘧啶（uracil）腺嘌呤（adenine）、鸟嘌呤（guanine）、胞嘧啶（cytosine）、胸腺嘧啶（thymine）磷酸phosphoricacidphosphoricacid

13.1核苷酸核苷酸（nucleotide）

磷酸＋核糖＋碱基核糖核苷酸（ribonucleotide）脱氧核糖核苷酸（deoxyribonucleotide）

磷酸＋脱氧核糖＋碱基pyrimidineandpurinepyrimidineandpurine稀有碱基(minorbases)

糖与碱基之间的C-N键称为N－糖苷键1’2’3’4’5’(OH)1’2’3’4’5’(OH)13.1.2核苷(nucleoside)－糖苷键碱基与糖环平面互相垂直核苷核苷酸＝核苷+磷酸（核苷酸是核苷的磷酸酯）核苷中戊糖C2'、C3'、C5'羟基可被磷酸酯化（脱氧核糖只有两个羟基可被磷酸酯化）13.1.3核苷酸(nucleotide)nucleotide细胞内游离核苷酸及其衍生物(1)

Nucleosidetriphosphates

ATP,GTP,CTPAMPADPATP~~(2)Cyclicnucleosidemonophosphate

3’,5’-cAMP3’,5’-cGMPSecondarymessengersincellsignaltransductions.GDP-galactose,GDP-glucose：glycosidoprotein

synthesisAdenosinediphosphate(ADP)ispartofmanycoenzymes,e.g.,coenzymeA,nicotinamideadeninedinucleotide(NAD+),flavinadeninedinucleotide(FAD).(3)Otherfunctions

Nucleotideandnomenclature中文名称英文名称英文简称5'－腺苷单磷酸5'-adenosinemonophosphateAMP5'－腺苷二磷酸5'-adenosinediphosphateADP5'－腺苷三磷酸5'-adenosinetriphosphateATP5'－脱氧腺苷单磷酸5'-deoxyadenosinemonophosphatedAMP3'5'－环化腺苷单磷酸3'5'-cyclicadenosinemonophosphatecAMP13.2核酸的共价结构Nucleicacidcovalentstructure13.2.1核酸中核苷酸的连接方式

核苷酸是核酸的结构单位Phosphodiesterbonds13.2.2TheprimarystructureofDNAThecovalentbackbonesofnucleicacidsconsistofalternating交互的phosphateandpentose(-D-deoxyriboseinDNA,-D-riboseinRNA)residues.DNARNA5′PdAPdCPdGPdTOH3′5′PAPCPGPUOH3′5′ACGT..............3′5′ACGU.........3′ACGT........ACGU.......5'→3'端T5’3’OHU5’3’OHOHOHOHOHTheprimarystructureofDNADNA一级结构的特点无分支的线形或环形链；DNA链很长，分子量很大，编码巨大的信息量；真核生物与原核生物具有不同的特性：真核生物具有断裂基因，有内含子，无操纵子，调控序列所占比例大，有大量重复序列原核生物无内含子，有操纵子，调控序列所占比例小，很少重复序列。。。。。13.2.3TheprimarystructureofRNAThe3’-hydroxylgroupofonenucleotideisjoinedtothe5’-hydroxylgroupofthenextnucleotidebyaphosphodiesterbridge.Thecovalentbackbonesofnucleicacidsconsistofalternatingphosphateandpentose(-D-deoxyriboseinDNA,-D-riboseinRNA)residues.Thecharacteristicbasescanberegardedassidegroupsattachingtothebackboneatregularintervals(similartotheRgroupsonapeptidechains).EachDNAandRNAstrandshaveaspecificpolaritywithadistinct5’end(theendlackinganucleotideatthe5’position)anda3’end(theendlackinganucleotideatthe3’position).ThebasesequenceofaDNAorRNAmoleculeisalwayswrittenwiththe5’endontheleftand3’endontherightbyconvention.TheprimarystructureofRNAThenucleotidesequencesofshortsegmentofnucleicacidscanberepresentedindifferentways.ThebackbonesofbothDNAandRNAarehydrophilic,havingnegativechargesatphysiologicalpH,thataregenerallyneutralizedbypositivelychargedproteins,metalions,andpolyaminesincells.TheprimarystructureofRNATheprimarystructureofRNA无分支的线形链；RNA种类核苷酸数目碱基组成3'端5'端其他特点tRNA73-93稀有碱基较多CpCpAOHpG或pC有保守序列5SrRNA120无稀有碱基5.8SrRNA160有修饰碱基核糖可被甲基化.........原核mRNA/无修饰碱基有一段非翻译区有一段非翻译区有多顺反子mRNA真核mRNA/有修饰碱基有poly(A)有5'端帽子单顺反子不同种类具有不同结构：TheprimarystructureofRNATheprimarystructureofRNAofProkaryotes

原核生物5´3´顺反子顺反子顺反子插入顺序插入顺序先导区末端顺序TheprimarystructureofRNAofEukaryota真核生物AAAAAAA-OH5´

“帽子”PolyA

3´

编码区m7G-5´ppp-N-3´p非编码区非编码区真核生物：绝大多数真核细胞mRNA3′端有长约20-250的多聚腺苷酸poly(A)是在转录后经poly(A)聚合酶的作用添加上去的poly(A)尾巴可能与mRNA从细胞核到细胞质的运输有关poly(A)还可能与mRNA的半寿期有关

TheprimarystructureofRNATheprimarystructureofRNA真核生物mRNA的5端帽子cap的功能抗5'核酸外切酶的降解作用有助于蛋白质合成过程中核糖体对mRNA的识别与结合，使翻译得以正确起始typeⅠ:m7G5′ppp5′NmpNp13.3DNA的高级结构

ThethreedimensionalstructuresofDNAChargaff’slaw:

A＝TG=CA+C=G+TA+G=C+TErwinChargaff

（1905－1995）不同生物DNA的碱基组成DNAfibrex-raydiffractionpattern

TheNobelPrizeinPhysiologyorMedicine1962"fortheirdiscoveriesconcerningthemolecularstructureofnucleicacidsanditssignificanceforinformationtransferinlivingmaterial"FrancisHarryComptonCrickJamesDeweyWatsonMauriceHughFrederickWilkins1/3oftheprize1/3oftheprize1/3oftheprizeUnitedKingdomUSAUnitedKingdomandNewZealandMRCLaboratoryofMolecularBiology

Cambridge,UnitedKingdomHarvardUniversity

Cambridge,MA,USALondonUniversity

London,UnitedKingdomb.1916

d.2004b.1928b.1916

(inPongaroa,NewZealand)

d.2004TheDNAmoleculeisaright-handeddoublehelixcontainingtwoantiparallelstrandsthatwindaroundthesameaxis.ThestructureofDNAdoublehelixThephosphate-deoxyribosebackbonesareontheoutsideofthehelix(forminga“hydrophilicsurface”),whereasthepurineandpyrimidinebasesarestackedinside.Theplanesofthebasesareperpendicular垂直的tothehelixandtheplanesofthedeoxyriboseringsarenearlyatrightanglestothoseofthebases.Thediameteroftheproposedhelixisabout20Å,adjacentbasesareseparatedby3.4Åandrelatedbyarotationofabout36withthehelicalstructurerepeatsaboutevery10residuesoneachchainatintervalsofabout34Å.2.0nmTheDNAmoleculecontainstwokindsofgrooves,amajorgroove(of~12Åwide)andaminorgroove(of~6Åwide),formedbecausetheglycosidicbondsofabasepairarenotdiametricallyoppositetoeachother.Thetwoantiparallelchainsarecomplementarytoeachotherthroughhydrogenbondsbetweenpairsofbases.Adenineisalwayspairedwiththymine(withtwoH-bonds),guaninewithcytosine(withthreeH-bonds).Thetwoantiparallelpolynucleotidechainsofdouble-helicalDNAarenotidenticalineitherbasesequenceorcomposition.Insteadtheyarecomplementarytoeachother.Thedouble-helicalmodelofDNAimmediatelysuggestedamechanismforthereplicationofDNA.Geneticinformationhastobereplicated.ThedoublehelixmodelforDNAisapairoftemplates,eachofwhichiscomplementarytotheother.Itwasproposedthatatreplication,theparentstrandsbecomeseparated(H-bondsarebroken),andeachformsthetemplateforbiosynthesisofacomplementarydaughterstrand.Thetwodouble-helicalDNAmoleculesareexactlythesameastheparentduplex(geneticinformationisthusreplicated).ThesecondarystructureofDNAThesecondarystructureofDNA基本数据：2.0nm小沟大沟平均直径2nm碱基堆积距离0.34nm相邻核苷酸夹角36o螺距3.4nmThesecondarystructureofDNATheDNAdoublehelixisheldtogetherbytwoforces:hydrogenbondingandbase-stackinginteractions.ThecomplementaritybetweentheDNAstrandsisattributabletothehydrogenbondingbetweenbasepairs.ForcesstabilizingDNAdoublehelixThebase-stackinginteractions,whicharelargelynonspecificwithrespecttotheidentityofthestackedbases,makethemajorcontributiontothestabilityofthedoublehelix.ForcesstabilizingDNAdoublehelix

③磷酸基上的负电荷与介质中的阳离子或组蛋白的正离子之间形成离子键，中和了磷酸基上的负电荷间的斥力，有助于DNA稳定。④碱基处于双螺旋内部的疏水环境中，可免受水溶性活性小分子的攻击。Forc