双语分子生物学
中北大学化工与环境学院生物工程专业 Molecular Biology (分子生物学),主讲: 张志军 博士、博导、副教授,埃博拉病毒,截至2014年8月26日，埃博拉已在塞拉利昂、利比亚和几内亚造成1427人死亡。 2014年8月9日，中国宣布已掌握埃博拉病毒抗体基因，同时具备对埃博拉病毒进行及时检测的诊断试剂研发能力，这让世界为之惊喜。,主要参考教材,PC Turner et al. Instant Notes in Molecular Biology (Second edition). BIOS Scientific Publishers Limited, 2000 分子生物学(第三版)导读版(精要速览系列) 朱玉贤，李毅，郑晓峰编著。现代分子生物学（第3版） 高等教育出版社 2007-11-1 Robert F. Weaver Molecular biology 2004. （Third edition）,分子生物学学习方法及注意问题,专心听讲 做好笔记 认真思考 学会归纳 注意纪律 预习复习,课程主要内容,1.1 Cellular classification 1.2 Subcellular organelles 1.3 Macromolecules 1.4 Large macromolecular assemblies,1. Cells and macromolecules,1.1 Cellular classification,Prokaryotes： Eubacteria (真细菌) Acchaea(古细菌) Eukaryotes： Plants Animals Fungi Protist(原生生物),Prokaryotes and eukaryotes,Schematic of a eukaryotic cell,Schematic of a prokaryotic cell,Differentiation (分化),1.2 Subcellular organelles (亚细胞器),Nuclei nucleoli（核仁）, nucleus Mitochondria and Chloroplasts Endoplasmic reticulum Microbodies Organelle isolation,Nuclei,Endoplasmic reticulum and ribosomes,Mitochondria and Chloroplasts,Microbodies: lysosome,1.3 Macromolecules,Proteins Nucleic acids Polysaccharides Lipids Complex macromolecules,Proteins polymers of amino acids, peptide bonds,Nucleic acids DNA and RNA, polymers of nucleotides, mRNA, tRNA, rRNA,Polysaccharides Polymers of simple sugars, glycoside bonds They functions mainly as nutritional sugar stores and as structural material. Cellulose, starch, chitin, mucopolysaccharides(黏多糖),Lipids Key components of membranes, protective coats and other structures. Glycerides (甘油酯), phospholipids(磷脂)，sphingolipids（鞘脂，如神经氨酰）,Complex macromolecules Nucleoproteins(核蛋白), ribozyme（核糖体） Glycoproteins Proteoglycans (mucoproteins)蛋白多糖（粘蛋白） Lipid-linked proteins glycolipids,1.4 Large macromolecular assemblies,Protein complexes Cytoskeleton: microtubules, microfilaments, intermediate filaments These organize the shape and movement of cells and subcellular organelles. Cilia and flagella (纤毛和鞭毛 ) are also composed of microtubules complexed with dynein and nexin（动力蛋白和连接蛋白 ）.,Nucleoproteins Bacterial 70S ribosomes: 50S larger subunit (23S and 5S RNA + 31 proteins)+30S small subunit (16S RNA + 21 proteins) Eukayotic 80S ribosomes: 60S larger subunit (28S, 5.8S and 5S RNAs + 31 proteins)+40S small subunits (18S RNA) Chromotin contains DNA and the basic histone proteins.,Membranes Membrane phospholipids and sphingolipids (鞘脂) form bilayers. Membrane proteins may be peripheral (外周的) or integral （整合的）and act as receptors, enzymes, transporters or mediators of cellular interaction.,Noncovalent interaction (非共价互作) Charge-charge (电荷) interactions Charge-dipole(偶极) and dipole-dipole interaction Hydrogen bonds 氢键 Hydrophobic interaction 疏水相互作用,思考题,试述原核和真核细胞的异同点。 亚细胞器主要有哪些？各自主要结构和功能是什么？ 生物大分子包括哪些？分别叙述其组成结构。 试举出三种大分子的组装形式。,2 Nucleic acid and Chromosome,Including,2.1 Properties of nucleic acid 2.2 Prokaryotic and Eukaryotic chromosome structure,2.1 Properties of nucleic acid,2.1.1 Nucleic acid structure 2.1.2 Chemical & physical properties 2.1.3 Spectroscopic (光谱学) & thermal （热力学） properties 2.1.4 DNA supercoiling,2.1.1 Nucleic acid structure Bases Nucleosides(核苷) base+sugar Nucleotides (核苷酸) base+sugar+phosphate Phosphodiester bonds,Bases DNA: adenine(A), guanine(G), cytosine(C), thymine(T) RNA: adenine(A), guanine(G), cytosine(C), uracil(U),DNA/RNA sequence Conventionally, DNA or RNA are represented by their single letter A, T, G, C or U. Write the sequences with 5'-end at the left. DNA: 5'-ATAAGCTC-3' or ATAAGCTC RNA: 5'-AUAGCUUGA-3' direction: ATAAG is not the same as GAATA,DNA double helix Base pairing Complementary base pairs Antiparallel minor groove; major groove right-handed (clockwise) B-form Overwound; underwound,· The B-form of DNA is a double helix consisting of two polynucleotide chains that run antiparallel. · The nitrogenous bases of each chain are flat purine or pyrimidine rings that face inwards and pair with one another by hydrogen bonding to form A-T or G-C pairs only. · The diameter of the double helix is 20 Å, and there is a complete turn every 34 Å, with 10 base pairs per turn. · The double helix forms a major (wide) groove and a minor (narrow) groove.,Key Concepts,A, B and Z helices,ZDNA：它是左手双螺旋，与右手螺旋的不同是螺距延长(4.5nm左右)，直径变窄(1.8nm)，每个螺旋含12个碱基对，分子长链中磷原子不是平滑延伸而是锯齿形排列，有如“之”字形一样，因此叫它Z构象，这一构象中的重复单位是二核苷酸而不是单核苷酸；而且ZDNA只有一个螺旋沟，它相当于B构象中的小沟，它狭而深，大沟则不复存在。 进一步的分析还证明，ZDNA的形成是DNA单链上出现嘌呤与嘧啶交替排列所成的。比如CGCGCGCG或者CACACACA。,不同右手双螺旋DNA的结构参数,双螺旋 碱基倾 碱基夹 碱基间距 螺距 每轮碱 小沟宽nm× 大沟宽nm× 角（°）角（°）/nm nm 基数 小沟宽nm 大沟宽nm B-DNA 0 36.0 0.337 3.4 10 0.57×0.75 1.17×0.85 C-DNA 6 38.0 0.331 3.1 9.3 0.48×0.79 1.05×0.75 D-DNA 45.0 0.303 0.13×0.67 0.89×0.58 A-DAN 20 32.7 0.256 2.8 11 1.10×0.28 0.27×1.35 总之，DNA的双螺旋结构永远处于动态平衡中，DNA分子构象的变化与糖基和碱基之间空间相对位置有关。,2.1.2 Chemical & physical properties of nucleic acid Stability of nucleic acids Hydrogen bonding Hydrophobic interactions and dipole-dipole interactions,Effect of acid Strong acid -hydrolyzed completely, HClO4, 1
