生物化学教学课件：Protein structure

1、Protein structure2017-09-262Peptide bond 肽键3Number of negatively charged residues (Asp + Glu): 9Number of positively charged residues (Arg + Lys): 17Lysozyme 溶菌酶Primary sequence of 129 residues:KVFGRCELAAAMKRHGLDNYRGYSLGNWVCAAKFESNFNTQATNRNTDGSTDYGILQINSRWWCNDGRTPGSRNLCNIPCSALLSSDITASVNCAKKIVSDGNGMN

2、AWVAWRNRCKGTDVQAWIRGCRLTheoretical pI: 9.32 (http:/cgi-bin/protparam/protparam)4a-helix(a-螺旋)b-sheet(b-折叠)Lysozyme structure (PDB 3LYM)5An a-helix in lysozyme: RCELAAAMKRH (color code: CNOS)The a helixTo make optimal use of internal hydrogen bonds.Every helical turn extends about 5.4 along the axis.

3、 Only right-handed helix.Every helical turn includes 3.6 residues, so that every residue turns 100 degrees.65.4 7Interaction between side chains of residue i and i+3 or i+4;Pro rarely appears in a-helix .An a-helix in lysozyme: RCELAAAMKRH 908Linus Pauling (1901-1994) got the Nobel Prize in Chemistr

4、y in 1954 “for his research into the nature of the chemical bond and its application to the elucidation of the structure of complex substances”.9Coiled-coil structure(Myosin II coiled-coil, PDB 2FXO)90 Heptad repeats (七元重复) in sequence: -(abcdefg)n-a,d: hydrophobic; e,g: oppositely charged. 10 abcde

5、fgAn example: coiled-coil from myosin II (PDB 2FXO)-MASMKEEFTRLKEALEKSEAR-(Myosin II coiled-coil, PDB 2FXO)-MASMKEE FTRLKEA LEKSEAR-11123 and 4-stranded coiled-coil are also possible.Figure adapted from Proteins: Structure, Function and Genetics 7:1-15, (1990).13Lysozyme structure (PDB 3LYM)a-helix(

6、a-螺旋)b-sheet(b-折叠)14The b-sheet15The b-sheet16The b sheets（反平行的）（平行的）1718Extremely colorful protein structures19Immunoglobulin 免疫球蛋白PDB: 1IGTdomain 结构域subunit 亚基20Protein quaternary structures （四级结构）2122Denaturation （变性）of proteinsA loss of three-dimensional structure sufficient to cause loss of fun

7、ction. (/biotech/resources/proteins/labManual/images/220_04_021.gif)23Most proteins can be denatured by heatingMedical sterilization.An exception is the thermophilic bacteria.24Chaotropic reagents disturb the hydrogen bond network in proteins. O NH2 C NH2 NH2+ Cl- NH2 C NH2Urea 尿素Guanidine hydrochlo

8、ride (GdnHCl) 盐酸胍251929年在波士顿召开的第13届国际生理学会上他提出蛋白质变性学说：认为天然蛋白质分子不是一长的直链而是一紧密的结构；这种结构是借肽键之外的其他键，将肽链的不同部分连接而形成的，所以容易被物理及化学的力所破坏，即从有规则的折叠排列形式变成不规则及松散的形式。这个学说对于研究蛋白质大分子的高级结构有重要价值。 吴宪 (18931959)26Protein sequence determines its tertiary structure.The Nobel Prize in Chemistry 1972 for his work on ribonuclea

9、se, especially concerning the connection between the amino acid sequence and the biologically active conformation”.Christian B. Anfinsen This is true for only a small number of proteins.27Misfolding (错误折叠) diseases/images/figure1.gifPrion diseases: mad cow disease (bovine spongiform encephalopathy, BSE), Creutzfeldt-Jakob disease in human, scrapie in sheep, e