理学类分子生物物理学.ppt

1、Molecular Biophysics,分子生物物理学,分子水平,研究生物体系物理学性质、行为,Biopolymers: Nucleic acid (DNA, RNA) Protein,Molecules in Biosystem,Saccharide Lipid,Other,PROTEIN STRUCTURE,1965年中国在世界上首次用化学方法 人工合成的蛋白质牛胰岛素,Secondary Structure,Primary Structure,Tertiary Structure,supersecondary Structure or motif,domain,Quaternary S

2、tructure,Hierarchy of Protein Structure by Linderstrm-Lang,Chiral,L alanine,COOH,CH3,NH2,H,Property of amino acid,zwitterion,Uncharged structure Minor component,Dipolar ion, or zwitterion Major component,Classificatory of amino acid based sidechains (R groups),?,Histidine,Protein Primary Structure,P

3、eptide bond,Backbone,Side chain,Amine/N terminus,Carboxyl/C terminus,Pauling i-(i+4) interactions between i and i+4 stabilize helix,Distortions of a-helices,The majority of a-helices in globular proteins are curved or distorted somewhat compared with the standard Pauling-Corey model. Why? The packin

4、g of buried helices against other secondary structure elements in the core of the protein Proline residues induce distortions of around 20 degrees in the direction of the helix axis,3. Solvent. Exposed helices are often bent away from the solvent region. This is because the exposed C=O groups tend t

5、o point towards solvent to maximise their H-bonding capacity, i.e. tend to form H-bonds to solvent as well as N-H groups.,310 helix introduction,Only 3.4% of the residues are involved in 310 helices, and nearly all those in helical segments containing i-i+3 hydrogen bonds.,Ideal (-74.0, -4.0) / foun

6、d (-71.0 and -18.0),CO-HN hydrogen bond: i-i+3,Standard 310 helix,Proline helix,Left handed helix 3.0 residues per turn pitch = 9.4 No hydrogen bonding in the backbone but helix still forms. Poly-glycine also forms this type of helix Collagen: high in Gly-Pro residues has this type of helical struct

7、ure,p-helices introduction,The pi helix is an extremely rare secondary structural element in proteins. the backbone C=O of residue i hydrogen bonds to the backbone HN of residue i+5.,i- - i + 5 H-bonds 2.8angstrom,the phi and psi angles of the pure pi helix ( -57.1, -69.7) lie at the very edge of an

8、 allowed, minimum energy region of the Ramachandran (phi, psi) map. the pi helix requires that the angle tau (N-Ca-C) be larger (114.9) than the standard tetrahedral angle of 109.5 degrees. the large radius of the pi helix means the polypeptide backbone is no longer in van der Waals contact across t

9、he helical axis forming an axial hole too small for solvent water to fill. side chains are more staggered than the ideal 3.10 helix but not as well as the alpha helix.,H-bond: 1-5,alpha-helix, surface of protein, barrier amphiphilic protein design projects by Degrado, USA,Helical wheel tools,Helix d

10、ipole,The partial charges on the amide hydrogen and carbonyl oxygen are shown in units of the elementary charge contributing to an overall dipole moment of 3.46 Debye units.,helix macrodipole,Sheet,20-28% (Kabsch Creighton, 1993),a repeating secondary structure,Parameters of secondary structure,n is

11、 the number of residues per helical turn r is the helical rise per residue (nm) p is the helical pitch (nm).,-139 and +135,Parallel sheet,Antiparallel sheet,Twists,about 30 degrees per residue in right-handed sense Left-handed: crossover angel Right-handed: progressive H-bond twist,Parallel sheets a

12、re less twisted than anti-parallel and are always buried.,Bulges,Beta-hairpin Crossover connection: right-handed left-handed,One residue backbone, two H-bonds,Strand connections,Turn,that serve to reverse the direction of the polypeptide chain Surface of the protein Antibody recognition, phosphoryla

13、tion, glycosylation, hydroxylation,Gamma-turn,H-bond: i-i+2 (70, -60) and (-70, 60) for i+1 residue,Type I and I turn,H-bond: i-i+3 (-60, -30) and (-90, 0) for i+1, i+2 residues,The backbone dihedral angles of residue are (-60, 120) and (80, 0) of residues i+1 and i+2, respectively of the type II tu

14、rn.,2.3.3. Type II and II turn,the hydrogen bond between CO of residue i and NH of residue i+3. This is a single turn of right-handed (III) and left-handed (III) 3.10 helix, respectively. The backbone dihedral angles of residue are (-60, -30) and (-60, -30) of residues i+1 and i+2, respectively of t

15、he classical type III turn.,2.3.4. Other structures,1. Loop random coil 2. Paperclips cap of a-helix,Identification of secondary structure,Identification without 3D structure,CD,可信度： a-helix, 97%; sheet 75%; 50% turn, 89% other From Manavalan b.-; c.-loop-; d. Rossmann折叠； E,f,g. 回形拓扑结构,细胞色素C,-loop-,

16、细胞核抗原的-结构,-,纤溶酶原的-loop-结构,结构域domain,多肽链在超二级结构的基础上进一步折叠成紧密的近乎于球状的结构，这种结构称为结构域domain,结构域的特点,（1）结构域是球状蛋白质的独立折叠单位。对一些较小的球状蛋白质分子或亚基来说，结构域和三级结构是一个意思。 例如红氧还蛋白，核糖核酸酶、肌红蛋白等。,（2）对于较大的球状蛋白质或亚基，其三级结构往往由两个或多个结构域缔合而成也即它们是多结构域的，例如免疫球蛋白的轻链含2个结构域。,结构域有时也指功能域。功能域可以是一个结构域，也可以是由两个结构域或两个以上结构域组成，从功能角度看许多多结构域的酶，其活性中心都位于结构域之间，因为通过结构域容易构建具有特定三维排布的活性中心。结构域之间常常只有一段柔性的肽链连接，形成所谓铰链区，使结构域容易发生相对运动，这是结构域的一大特点。结构域之间的这种柔性将有利于活性中心结合底物和施加应力。,Protein Tertiary Structure,三级结构指一个不可分的单元（分子）的完整的三维空间结构。对于蛋白质，此单元通常是共价连接的一个分子。,目前已经测出三级结构的生物大分子都储存在蛋白质数据库中（Protein data bank,PDB)，借助软件可查阅显示其空间结构，还可以在不同方向旋转以获得空间结构的细节。,嗜热菌蛋白