第13章 核酸的結構

第十三章核酸的結構StructureofNucleicAcid核酸的化學組成：核苷酸（nucleotide）

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

核糖核苷酸（ribonucleotide）脫氧核糖核酸（DNA）

脫氧核糖核苷酸（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兩類核酸的基本化學組成RNADNA組成戊糖核糖（D-ribose）脫氧核糖（D-2-deoxyribose）堿基腺嘌呤（adenine）、鳥嘌呤（guanine）、胞嘧啶（cytosine）尿嘧啶（uracil）腺嘌呤（adenine）、鳥嘌呤（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＋堿基核糖核苷酸（ribonucleotide）脫氧核糖核苷酸（deoxyribonucleotide）

磷酸＋脫氧核糖＋堿基pyrimidineandpurinepyrimidineandpurine稀有堿基(minorbases)

糖與堿基之間的C-N鍵稱為N－糖苷鍵1’2’3’4’5’(OH)1’2’3’4’5’(OH)13.1.2核苷(nucleoside)－糖苷鍵堿基與糖環(huán)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'羥基可被磷酸酯化（脫氧核糖只有兩個羥基可被磷酸酯化）13.1.3核苷酸(nucleotide)nucleotide細胞內(nèi)游離核苷酸及其衍生物(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中文名稱英文名稱英文簡稱5'－腺苷單磷酸5'-adenosinemonophosphateAMP5'－腺苷二磷酸5'-adenosinediphosphateADP5'－腺苷三磷酸5'-adenosinetriphosphateATP5'－脫氧腺苷單磷酸5'-deoxyadenosinemonophosphatedAMP3'5'－環(huán)化腺苷單磷酸3'5'-cyclicadenosinemonophosphatecAMP13.2核酸的共價結構Nucleicacidcovalentstructure13.2.1核酸中核苷酸的連接方式

核苷酸是核酸的結構單位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一級結構的特點無分支的線形或環(huán)形鏈；DNA鏈很長，分子量很大，編碼巨大的信息量；真核生物與原核生物具有不同的特性：真核生物具有斷裂基因，有內(nèi)含子，無操縱子，調(diào)控序列所占比例大，有大量重復序列原核生物無內(nèi)含子，有操縱子，調(diào)控序列所占比例小，很少重復序列。。。。。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無分支的線形鏈；RNA種類核苷酸數(shù)目堿基組成3'端5'端其他特點tRNA73-93稀有堿基較多CpCpAOHpG或pC有保守序列5SrRNA120無稀有堿基5.8SrRNA160有修飾堿基核糖可被甲基化.........原核mRNA/無修飾堿基有一段非翻譯區(qū)有一段非翻譯區(qū)有多順反子mRNA真核mRNA/有修飾堿基有poly(A)有5'端帽子單順反子不同種類具有不同結構：TheprimarystructureofRNATheprimarystructureofRNAofProkaryotes

原核生物5′3′順反子順反子順反子插入順序插入順序先導區(qū)末端順序TheprimarystructureofRNAofEukaryota真核生物AAAAAAA-OH5′

“帽子”PolyA

3′

編碼區(qū)m7G-5′ppp-N-3′p非編碼區(qū)非編碼區(qū)真核生物：絕大多數(shù)真核細胞mRNA3′端有長約20-250的多聚腺苷酸poly(A)是在轉錄后經(jīng)poly(A)聚合酶的作用添加上去的poly(A)尾巴可能與mRNA從細胞核到細胞質的運輸有關poly(A)還可能與mRNA的半壽期有關

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質合成過程中核糖體對mRNA的識別與結合，使翻譯得以正確起始typeⅠ:m7G5′ppp5′NmpNp13.3DNA的高級結構

ThethreedimensionalstructuresofDNAChargaff’slaw:

A＝TG=CA+C=G+TA+G=C+TErwinChargaff

（1905－1995）不同生物DNA的堿基組成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.Thediameteroftheproposedhelixisabout20?,adjacentbasesareseparatedby3.4?andrelatedbyarotationofabout36withthehelicalstructurerepeatsaboutevery10residuesoneachchainatintervalsofabout34?.2.0nmTheDNAmoleculecontainstwokindsofgrooves,amajorgroove(of~12?wide)andaminorgroove(of~6?wide),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基本數(shù)據(jù)：2.0nm小溝大溝平均直徑2nm堿基堆積距離0.34nm相鄰核苷酸夾角36o螺距3.4nmThesecondarystructureofDNATheDNAdoublehelixisheldtogetherbytwoforces:hydrogenbondingandbase-stackinginteractions.ThecomplementaritybetweentheDNAstrandsisattributabletothehydrogenbondingbetweenbasepairs.ForcesstabilizingDNAdoublehelixThebase-stackinginteractions,whicharelargelynonspecificwithrespecttotheidentityofthestackedbases,makethemajorcontributiontothestabilityofthedoublehelix.ForcesstabilizingDNAdoublehelix

③磷酸基上的負電荷與介質中的陽離子或組蛋白的正離子之間形成離子鍵，中和了磷酸基上的負電荷間的斥力，有助于DNA穩(wěn)定。④堿基處于雙螺旋內(nèi)部的疏水環(huán)境中，可免受水溶性活性小分子的攻擊。Forc