第13章 核酸的結(jié)構(gòu)

1、第十三章第十三章 核酸的結(jié)構(gòu)核酸的結(jié)構(gòu)Structure of Nucleic Acid核酸的化學(xué)組成： 核苷酸（nucleotide） 核酸（nucleic acid）磷酸（phosphoric acid）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）The nucleic acids (DNA and RNA) are The nucleic acids (DNA and RNA) are polymers of nucle

2、otide unitspolymers of nucleotide units DNA consists of four kinds of deoxyribonucleotide units linked together through covalent bonds. Each nucleotide unit is made of a nitrogenous base (the various part in the four different deoxyribonucleotides), a pentose sugar, and a phosphate group. The nitrog

3、enous base can be adenine (A), guanine (G), cytosine (C), or thymine (T). The nitrogenous bases are derivatives衍生物衍生物 of two parent compounds, pyrimidine and purine. The carbon and nitrogen atoms in the pyrimidine and purine rings are numbered. H 兩類核酸的基本化學(xué)組成兩類核酸的基本化學(xué)組成RNADNA組組成成戊糖戊糖核糖核糖（D-ribose）脫氧核

4、糖脫氧核糖（D-2-deoxyribose）堿基堿基腺嘌呤腺嘌呤（adenine）、）、 鳥嘌呤鳥嘌呤（guanine）、胞嘧啶胞嘧啶（cytosine）尿嘧啶尿嘧啶（uracil）腺嘌呤腺嘌呤（adenine）、）、鳥嘌呤鳥嘌呤（guanine）、）、胞嘧啶胞嘧啶（cytosine）、）、胸腺嘧啶胸腺嘧啶（thymine）磷酸磷酸phosphoric acidphosphoric acid 13.113.1核苷酸核苷酸核苷酸（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pyrimidi

5、ne and purinepyrimidine and purine稀有堿基稀有堿基( (minor bases) 糖與堿基之間的C-N鍵稱為N糖苷鍵(OH)(OH)13.1.2 核苷核苷 (nucleoside)糖苷鍵堿基與糖環(huán)平面互相垂直核苷核苷核苷酸核苷核苷酸核苷+ +磷酸（核苷酸是核苷的磷酸酯）磷酸（核苷酸是核苷的磷酸酯）核苷中戊糖核苷中戊糖C C22、C C33、C C55羥基可被磷酸酯化（脫氧核糖羥基可被磷酸酯化（脫氧核糖只有兩個羥基可被磷酸酯化）只有兩個羥基可被磷酸酯化）13.13.1.3 1.3 核苷酸核苷酸 (nucleotide)(nucleotide)nucleotide

6、HHCH2OHOHHHOHHCH2OHOHHHONNNNNNONH2NH2HH195腺嘌呤核苷酸3胞嘧啶脫氧核苷酸HOPO-OOPO-OO細(xì)胞內(nèi)游離核苷酸及其衍生物(1)(1) Nucleoside Nucleoside triphosphatestriphosphates ATP,GTP,CTPATP,GTP,CTPO-POO-NNNNN H2OHHO HHO HHO C H2O-POO-O-POO-三磷酸腺苷 (ATP)AMPADPATP(2) (2) Cyclic nucleoside Cyclic nucleoside monophosphatemonophosphate 3,5-cA

7、MP3,5-cGMPSecondary messengers in cell signal transductions.GDP-galactose, GDP-glucose：glycosidoprotein synthesis Adenosine diphosphate (ADP) is part of many coenzymes, e.g., coenzyme A, nicotinamide adenine dinucleotide (NAD+), flavin adenine dinucleotide (FAD).(3)Other functions Nucleotide and nom

8、enclatureNucleotide and nomenclature中文名稱中文名稱英文名稱英文名稱英文簡稱英文簡稱55腺苷單磷酸腺苷單磷酸5-adenosine 5-adenosine monophosphatemonophosphateAMPAMP55腺苷二磷酸腺苷二磷酸5-adenosine 5-adenosine diphosphatediphosphateADPADP55腺苷三磷酸腺苷三磷酸5-adenosine 5-adenosine triphosphatetriphosphateATPATP55脫氧腺苷單脫氧腺苷單磷酸磷酸5-deoxyadenosine 5-deoxyad

9、enosine monophosphatemonophosphatedAMPdAMP3535環(huán)化腺苷環(huán)化腺苷單磷酸單磷酸35-cyclic adenosine 35-cyclic adenosine monophosphatemonophosphatecAMPcAMP13.2 13.2 核酸的共價結(jié)構(gòu)核酸的共價結(jié)構(gòu)Nucleic acid covalent structureNucleic acid covalent structure13.2.1 13.2.1 核酸中核苷酸的連接方式核酸中核苷酸的連接方式 核苷酸是核酸的結(jié)構(gòu)單位核苷酸是核酸的結(jié)構(gòu)單位Phosphodiester bonds1

10、3.2.2 13.2.2 The primary structure of DNAThe primary structure of DNAThe covalent backbones of nucleic acids consist of alternating 交互的交互的phosphate and pentose ( -D-deoxyribose in DNA, -D-ribose in RNA) residues.DNA RNA5PdAPdCPdGPdTOH 3 5PAPCPGPUOH 3 5ACGT. 3 5ACGU. 3 ACGT. ACGU.5533端端 T53OH U53OH O

11、H OH OH OH The primary structure of DNAHHH2COHHHOOPOHOCHHH2COHHHOOPOHOTHHH2COHHHOOPOHOGHHH2COHHHOOPOHOAODNADNA一級結(jié)構(gòu)的特點一級結(jié)構(gòu)的特點無分支的線形或環(huán)形鏈無分支的線形或環(huán)形鏈；DNADNA鏈很長，分子量很大，編碼巨大的信息量；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)序列子，調(diào)控序列所占比例大，有大量重復(fù)序列原

12、核生物無內(nèi)含子，有操縱子，調(diào)控序列所原核生物無內(nèi)含子，有操縱子，調(diào)控序列所占比例小，很少重復(fù)序列。占比例小，很少重復(fù)序列。13.2.3 13.2.3 The primary structure of RNAThe primary structure of RNA The 3-hydroxyl group of one nucleotide is joined to the 5-hydroxyl group of the next nucleotide by a phosphodiester bridge. The covalent backbones of nucleic acids cons

13、ist of alternating phosphate and pentose ( -D-deoxyribose in DNA, -D-ribose in RNA) residues.NNNNNH2OOHHHHCH3HONHNH2ONOOHHHHCH2HOHPOOHOHHHPOOOHNNNNOOOHHHHCH2HONOONOOHOHHHCH2HONH2POOHOHHHPOOOHHH The characteristic bases can be regarded as side groups attaching to the backbone at regular intervals (si

14、milar to the R groups on a peptide chains). Each DNA and RNA strands have a specific polarity with a distinct 5 end (the end lacking a nucleotide at the 5 position) and a 3 end (the end lacking a nucleotide at the 3 position). The base sequence of a DNA or RNA molecule is always written with the 5 e

15、nd on the left and 3 end on the right by convention.The primary structure of RNAThe primary structure of RNA The nucleotide sequences of short segment of nucleic acids can be represented in different ways. The backbones of both DNA and RNA are hydrophilic, having negative charges at physiological pH

16、, that are generally neutralized by positively charged proteins, metal ions, and polyamines in cells.The primary structure of RNAThe primary structure of RNAThe primary structure of RNAThe primary structure of RNA 無分支的線形鏈；無分支的線形鏈；RNARNA種種類類核苷酸核苷酸數(shù)目數(shù)目堿基組成堿基組成33端端55端端其他特點其他特點tRNAtRNA73-9373-93稀有堿基較多稀有

17、堿基較多CpCpAOHCpCpAOHpGpG或或pCpC有保守序列有保守序列5 S 5 S rRNArRNA120120無稀有堿基無稀有堿基5.8 S 5.8 S rRNArRNA160160有修飾堿基有修飾堿基核糖可被甲基化核糖可被甲基化.原核原核mRNAmRNA/ /無修飾堿基無修飾堿基有一段非有一段非翻譯區(qū)翻譯區(qū)有一段有一段非翻譯非翻譯區(qū)區(qū)有多順反子有多順反子mRNAmRNA真核真核mRNAmRNA/ /有修飾堿基有修飾堿基有有poly(Apoly(A) )有有55端端帽子帽子單順反子單順反子不同種類具有不同結(jié)構(gòu)不同種類具有不同結(jié)構(gòu)：The primary structure of RN

18、AThe primary structure of RNAThe primary structure of RNA of ProkaryotesThe primary structure of RNA of Prokaryotes 原核生物原核生物53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The primary structure of RNA of The primary structure of RNA of EukaryotaEukaryota真核生物真核生物AAAAAAA-OH5 “帽子帽子”PolyA 3 編碼區(qū)編碼區(qū)m7G-5 ppp-N-3 p非編碼區(qū)非編碼區(qū)非編碼區(qū)非

19、編碼區(qū)真核生物：絕大多數(shù)真核細(xì)胞真核生物：絕大多數(shù)真核細(xì)胞mRNA3mRNA3端有長端有長 約約20- 25020- 250的多聚腺苷酸的多聚腺苷酸poly(Apoly(A) )是在轉(zhuǎn)錄后經(jīng)是在轉(zhuǎn)錄后經(jīng)poly(Apoly(A) )聚合酶的作用聚合酶的作用 添加上去的添加上去的poly(Apoly(A) )尾巴可能與尾巴可能與mRNAmRNA從細(xì)胞核到細(xì)胞質(zhì)從細(xì)胞核到細(xì)胞質(zhì) 的運輸有關(guān)的運輸有關(guān)poly(Apoly(A) )還可能與還可能與mRNAmRNA的半壽期有關(guān)的半壽期有關(guān)The primary structure of RNAThe primary structure of RNATh

20、e primary structure of RNAThe primary structure of RNA真核生物真核生物mRNAmRNA的的5 5端帽子端帽子capcap的功能的功能抗抗55核酸外切酶的降解作用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有助于蛋白質(zhì)合成過程中核糖體對mRNAmRNA的識的識別與結(jié)合，使翻譯得以正確起始別與結(jié)合，使翻譯得以正確起始type: mtype: m7 7 G G55ppp ppp 55NmpNpNmpNp13.3 13.3 DNADNA的高級結(jié)構(gòu)的高級結(jié)構(gòu) The three dimensional structures of DNAThe

21、three dimensional structures of DNAChargaffs law: AT G = C A+C = G+T A+G = C+TErwin Chargaff （19051995）不同生物不同生物DNADNA的堿基組成的堿基組成DNA DNA fibrefibre x-ray diffraction pattern x-ray diffraction pattern The Nobel Prize in Physiology or Medicine 1962for their discoveries concerning the molecular structure

22、 of nucleic acids and its significance for information transfer in living materialFrancis Harry Compton CrickJames Dewey WatsonMaurice Hugh Frederick Wilkins1/3 of the prize1/3 of the prize1/3 of the prizeUnited KingdomUSAUnited Kingdom and New ZealandMRC Laboratory of Molecular Biology Cambridge, U

23、nited KingdomHarvard University Cambridge, MA, USALondon University London, United Kingdomb. 1916d. 2004b. 1928b. 1916(in Pongaroa, New Zealand)d. 2004 The DNA molecule is a right-handed double helix containing two antiparallel strands that wind around the same axis.The structure of DNA double helix

24、The structure of DNA double helix The phosphate-deoxyribose backbones are on the outside of the helix (forming a “hydrophilic surface”), whereas the purine and pyrimidine bases are stacked inside. The planes of the bases are perpendicular垂垂直的直的 to the helix and the planes of the deoxyribose rings ar

25、e nearly at right angles to those of the bases. The diameter of the proposed helix is about 20 , adjacent bases are separated by 3.4 and related by a rotation of about 36 with the helical structure repeats about every 10 residues on each chain at intervals of about 34 .2.0 nm The DNA molecule contai

26、ns two kinds of grooves, a major groove (of 12 wide) and a minor groove (of 6 wide), formed because the glycosidic bonds of a base pair are not diametrically opposite to each other. The two antiparallel chains are complementary to each other through hydrogen bonds between pairs of bases. Adenine is

27、always paired with thymine (with two H-bonds), guanine with cytosine (with three H-bonds).l The two antiparallel polynucleotide chains of double-helical DNA are not identical in either base sequence or composition. Instead they are complementary to each other.lThe double-helical model of DNA immedia

28、tely suggested a mechanism for the replication of DNA. Genetic information has to be replicated. The double helix model for DNA is a pair of templates, each of which is complementary to the other. It was proposed that at replication, the parent strands become separated (H-bonds are broken), and each

29、 forms the template for biosynthesis of a complementary daughter strand. The two double-helical DNA molecules are exactly the same as the parent duplex (genetic information is thus replicated).The secondary structure of DNAThe secondary structure of DNAThe secondary The secondary structure structure

30、 of DNAof DNA基本數(shù)據(jù)：基本數(shù)據(jù)：2.0 nm小小溝溝大大溝溝平均直徑平均直徑2 nm堿基堆積堿基堆積距離距離0.34 nm相鄰核苷相鄰核苷酸夾角酸夾角36o螺距螺距3.4 nmThe secondary The secondary structure of DNAstructure of DNAlThe DNA double helix is held together by two forces: hydrogen bonding and base-stacking interactions. The complementarity between the DNA strand

31、s is attributable to the hydrogen bonding between base pairs. Forces stabilizing DNA double helix Forces stabilizing DNA double helix The base-stacking interactions, which are largely nonspecific with respect to the identity of the stacked bases, make the major contribution to the stability of the d

32、ouble helix.Forces stabilizing DNA double helixForces stabilizing DNA double helix 磷酸基上的負(fù)電荷與介質(zhì)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中的陽離子或組蛋白的正離子之間形成子之間形成離子鍵離子鍵，中和了，中和了磷酸基上的負(fù)電荷間的斥力，磷酸基上的負(fù)電荷間的斥力，有助于有助于DNADNA穩(wěn)定。穩(wěn)定。堿基處于雙螺旋內(nèi)部的堿基處于雙螺旋內(nèi)部的疏疏水環(huán)境中水環(huán)境中，可免受水溶性活，可免受水溶性活性小分子的攻擊。性小分子的攻擊。Forces stabilizing DNA double helix Forces stabilizing DNA double helix Meaning of double helixMeaning of double helix DNADNA的結(jié)構(gòu)可受環(huán)境條件的影響而改變的結(jié)構(gòu)可受環(huán)境條件的影響而改變B B型型（相對濕度（相對濕度92%92%）A A型型C C型型Z Z型（左手型（左手）P489P489表表13-613-6三種類型三種類型DNADNA的比較的比較三股螺旋三股螺旋H-DNAH-DNA13.3.3 13.3.3 DNADNA的三級結(jié)構(gòu)的三級結(jié)構(gòu)DNADNA在雙螺旋的基礎(chǔ)上通過扭曲和折疊形成的構(gòu)象在雙螺旋的基礎(chǔ)上通過扭曲和