科恩伯格现年59岁，目前供职 于美国斯坦福大学医学院，他 的父亲阿瑟科恩伯格是1959年 的诺贝尔医学或生理学奖得主 之一。科恩伯格揭示了真核生 物体内的细胞如何利用基因内 存储的信息生产蛋白质，而理 解这一点具有医学上的“基础性” 作用，因为人类的多种疾病如 癌症、心脏病等都与这一过程 发生紊乱有关。2006年化学诺贝尔奖罗杰科恩伯格 H1 The genetic code H2 Protein synthesis(translation) in prokaryotes H3 Translation in eukaryotes H4 Protein targeting H5 Protein glycosylationH protein synthesis The genetic code is a triplet code The genetic code is degenerate Universality of the genetic code Reading frames Open reading framesH1 The genetic code1. Triplet code The relationship between the nucleotide sequence of the mRNA and the amino acid sequence of the polypeptide is called the genetic code.Triplet code The three nucleotides in group called codon 43=64 codons Initiation codon (AUG) stop codon ( UAA, UAG,UGA) New codon: UGA Se-cysteineTriplet code2.The genetic code is degenerate There are 64 codons, but only 20 amino acids. Degenerate: A single amino acid is coded for by several different codons. Synonyms: Different codons that specify the same amino acid.Degeneracy of the genetic codeCodon and anticodon Anticodon: a triplet of bases in a specific tRNA molecule. Each base in the codon base pairs with its complementary base in the anticodon. Wobble base-pairing3.Universality of the genetic code All living organism used almost the same code. But there are a few differences. E.g. in mitochondrial mRNAs,some codons have different meanings.Different code4.Reading frames Start: UAG Stop: UAA, UAG, UGA Unit: Triplet Character: Continuousmutant5.Open reading frames An open reading frame (ORE) is a run of codons that starts with ATG and ends with a termination codon, TGA TAA or TAG. To identify potential coding regions. Coding regions of genes contain relatively long ORFs unlike noncoding DNA where ORFs are comparatively short. Overview Synthesis of aminoacyl-tRNA Initiation of protein synthesis Elongaion TerminationH2 translation in prokaryotes1. Overview Direction: mRNA: 53, Protein: NC Site: ribosome Recognizing: Codon (mRNA) base pairs anticodon (tRNA) via hydrogen bonding Translation phase: initiation, elongation and termination.2. Synthesis of aminoacyl-tRNA(amino acid activation)Each tRNA molecule has a cloverleaf secondary structure consisting of three stem loops, one of which bears the anticodon at its end. The amino acid is covalently bound to the 3 OH group at the 3 end by aminoacyl synthetase to form aminoacyl-tRNA. The reaction is called amino acid activation. tRNAGly Gly-tRNAGlyQuestion There are 61codons, 20 amino acids. How many are there tRNA and aminoacyl-tRNA synthetase?Synthesis of aminoacyl-tRNA is crucially important for two reasons First : each amino acid must be covalently linked to a tRNA molecule in order to take part in protein synthesis,which depend upon the adaptor function of tRNA. Second: the covalent bond is a high energy bond that enables the amino acid to react with the end of the growing polypeptide chain.The synthesis reaction occurs in two steps The first step is the reaction of amino acid and ATP to form an aminoacyl-AMP. The second step is the aminoacyl group of aminoacyl-AMP is transferred to the 3end of the tRNA molecule to form aminoacyl- tRNA.step oneStep two: Aminoacyl-AMP+tRNA-aminoacyl-tRNA +AMP3.Initiation of protein synthesis Each ribosome has three binding sites for tRNAs; an A site where the incoming aminoacyl-tRNA binds, a P site where the tRNA linked to the growing polypeptide chain is bound, and an E site which binds tRNA prior to its release from the ribosome . Translation in prokaryotes begins by the formation of a 30S initiation complex between the 30S ribosomal subunit, mRNA, initiation factors and fMet tRNA fmet . The 30S subunit binds to the Shine-Dalgarno sequence which lies 5 to the AUG Start codon and is complementary to the 16S rRNA of the small ribosomal subunit.Initiation The ribosome then moves in a 3 direction along the mRNA until it encounters the AUG codon. The 50S ribosomal subunit now binds to the 30S initiation complex to form the 70S initiation complex. In this complex, the anticodon of the fMet-tRNA fMet is base-paired to the AUG initiation codon (start codon) in the P site. InitiationfMet-tRNAfMet4. Elongation Elongation of the polypeptide chain occurs in three steps: 1.Aminoacyl-tRNA binding 2.Peptide bond formation 3.TranslocationElongation Factor Tu(EF-Tu)5.Termination Termination codons: UAA, UAG, UGA Release factors: RF1, RF2, RF3 RF1 UAA,UAG RF2 UGA RF3 RF3Protein synthesis in E.coli Initiation Elongation TerminationH3 Translation in eukaryotesComparison of protein synthesis in prokaryotes and eukaryotesprokaryoticEukaryoticcharacterPolycistron SD sequence AGGAGGU fMet-tRNAfMet EF-Tu, EF- Ts, EF-G RF1, RF2, RF3Monocistron Kozak sequence ACCAU