第13章 核酸的結(jié)構(gòu)

第十三章核酸的結(jié)構(gòu)StructureofNucleicAcid核酸的化學(xué)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(xué)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(gè)羥基可被磷酸酯化）13.1.3核苷酸(nucleotide)nucleotide細(xì)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(jià)結(jié)構(gòu)Nucleicacidcovalentstructure13.2.1核酸中核苷酸的連接方式

核苷酸是核酸的結(jié)構(gòu)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(jié)構(gòu)的特點(diǎn)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(fù)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(fù)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(diǎn)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(jié)構(gòu)：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(dǎo)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(xì)胞mRNA3′端有長約20-250的多聚腺苷酸poly(A)是在轉(zhuǎn)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(xì)胞核到細(xì)胞質(zhì)的運(yùn)輸有關(guān)poly(A)還可能與mRNA的半壽期有關(guān)

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(zhì)合成過程中核糖體對mRNA的識(shí)別與結(jié)合，使翻譯得以正確起始typeⅠ:m7G5′ppp5′NmpNp13.3DNA的高級結(jié)構(gòu)

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(fù)電荷與介質(zhì)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(fù)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