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Protein Structure

Protein Structure. Timothy G. Standish, Ph. D. The Genetic Code. Neutral Non-polar Polar Basic Acidic. S E C O N D B A S E. U. C. A. G. UUU UUC UUA UUG. UCU UCC UCA UCG. UAU UAC UAA UAG. UGU UGC UGA UGG. F I R S T B A S E. U. U C A G. T H I R D B

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Protein Structure

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  1. Protein Structure Timothy G. Standish, Ph. D.

  2. The Genetic Code Neutral Non-polar Polar Basic Acidic S E C O N D B A S E U C A G UUU UUC UUA UUG UCU UCC UCA UCG UAU UAC UAA UAG UGU UGC UGA UGG F I R S T B A S E U U C A G T H I R D B A S E Phe Tyr Cys Ser Stop Leu Stop Trp CUU CUC CUA CUG CCU CCC CCA CCG CAU CAC CAA CAG CGU CGC CGA CGG C U C A G His Leu Pro Arg Gln† AUU AUC AUA AUG ACU ACC ACA ACG AAU AAC AAA AAG AGU AGC AGA AGG U C A G A Asn† Ser Ile Thr Lys Arg †Have amine groups Met/ start GUU GUC GUA GUG GCU GCC GCA GCG GAU GAC GAA GAG GGU GGC GGA GGG U C A G G Asp Val Ala Gly* *Listed as non-polar by some texts Glu

  3. O O Alanine Cysteine C H2N C H2N OH OH Generic C C H H H H C C O Amine Acid H HS H H Non-polar C Polar H2N OH C O O Aspartic acid ? Histidine R H C H2N C H2N OH OH C C H H H H C C O C H H Basic C Acid OH NH C C H+N Different Amino Acid Classes

  4. O O O Glycine Alanine Leucine Valine O C C C H2N H2N H2N OH OH OH C H2N C C C OH H H C H H H H H C C H H C CH3 H H3C C H H CH3 H3C O O Methionine Isoleucine Phenylalanine O Tryptophan C C O H2N H2N OH OH C C C H2N H H3C OH C H2N O OH Proline H H C C C H H H C H H2N+ H C H H C C C OH H C H2C C H H H S H3C H H H2C CH2 H3C NH Non-PolarAmino Acids

  5. O Threonine O O Serine C H2N OH C C H2N H2N OH OH C H C C H Cysteine H H C H H H C C OH C O HS H Tyrosine CH3 O HO Glutamine H H C H2N C OH H2N O OH C Asparagine H C H C H H2N C OH H C H C H H H C H C O C H O C H NH2 HO NH2 Polar Amino Acids

  6. Glutamic acid Aspartic acid O C H2N O OH C H C H2N OH H C H C H H C H C O C H O C H OH OH Acidic Amino Acids

  7. Histidine O O Lysine Arginine C C H2N H2N OH OH C C H H H H C C H H H H C C H H H H C C H O H H C N C H2N +H2N H H C +H3N OH C H NH2 H C H C NH C C H+N Basic Amino Acids

  8. Levels Of Protein Organization • Primary Structure - The sequence of amino acids in the protein • Secondary Structure - The formation of a helices and b pleated sheets due to hydrogen bonding between the peptide backbone • Tertiary Structure - Folding of helices and sheets influenced by R groups • Quaternary Structure - The association of more than one polypeptide into a protein complex influenced by R groups

  9. Levels Of Protein OrganizationPrimary Structure Met-Gly-Ala-Pro-His-Ile-Asp-Glu-Met-Ser-Thr-...

  10. Glyceraldehyde-3-Phosphate Dehydrogenase Primary Structure • The Mycoplasma genitalium G-3P dehydrogenase protein sequence: • MAAKNRTIKV AINGFGRIGR LVFRSLLSKA NVEVVAINDL TQPEVLAHLL KYDSAHGELK RKITVKQNIL QIDRKKVYVF SEKDPQNLPW DEHDIDVVIE STGRFVSEEG ASLHLKAGAK RVIISAPAKE KTIRTVVYNV NHKTISSDDK IISAASCTTN CLAPLVHVLE KNFGIVYGTM LTVHAYTADQ RLQDAPHNDL RRARAAAVNI VPTTTGAAKA IGLVVPEANG KLNGMSLRVP VLTGSIVELS VVLEKSPSVE QVNQAMKRFA SASFKYCEDP IVSSDVVSSE YGSIFDSKLT NIVEVDGMKL YKVYAWYDNE SSYVHQLVRV VSYCAKL

  11. Protein Secondary Structure • The peptide backbone of DNA has areas of positive charge and negative charge • These areas can interact with one another to form hydrogen bonds • The result of these hydrogen bonds are two types of structures: • a helices • b pleated sheets

  12. H N C H C H + N O C C N H O - C C N H H O O O C H N C N C OH C H O C C N H H H C H H C C C O N H H HO H H C C N C O O Protein Secondary Structure:a Helix

  13. H N H C C N O H + C C O N H - C C N H H O O O C H H N C N C OH C O N C C H H H C H H C C C O N H H HO H H C C N C O O Protein Secondary Structure:a Helix

  14. R R R R R R R R R R R R R R Protein Secondary Structure:a Helix R groups stick out from the a helix influencing higher levels of protein organization

  15. M L S L R Q S First 12 residues are sufficient for transport to the mitochondria I R F F K P A T R T L C S S R Y L P Yeast Cytochrome C Oxidase Subunit IV Leader Neutral Non-polar Polar Basic Acidic • This leader sequence probably forms an a helix • This would localize specific classes of amino acids in specific parts of the helix • There are about 3.6 amino acids per turn of the helix with a rise of 0.54 nm per turn MLSLRQSIRFFKPATRTLCSSRYLL

  16. O O O O H H H H C C C C N N N N C C C C C C C C C C C C N N N N H H H H O O O O O O O O H H H H N N N N C C C C C C C C C C C C N N N N C C C C H H H H O O O O Protein Secondary Structure:b Pleated Sheet

  17. O O O O O O O O H H H H H H H H C C C C C C C C N N N N N N N N C C C C C C C C C C C C C C C C C C C C C C C C N N N N N N N N H H H H H H H H O O O O O O O O O O O O H H H H N N N N C C C C C C C C C C C C N N N N C C C C H H H H O O O O Protein Secondary Structure:b Pleated Sheet

  18. Levels Of Protein OrganizationTertiary Structure • Tertiary structure results from the folding of a helices and b pleated sheets • Factors influencing tertiary structure include: • Hydrophobic/hydrophilic interactions • Hydrogen bonding • Disulfide linkages • Folding by chaperone proteins

  19. G-3-P DehydrogenaseTertiary Structure Picture source: SWISS-PROT

  20. Levels Of Protein OrganizationQuaternary Structure • Quaternary structure results from the interaction of independent polypeptide chains • Factors influencing quaternary structure include: • Hydrophobic/hydrophilic interactions • Hydrogen bonding • The shape and charge distribution on associating polypeptides

  21. G-3-P Dehydrogenasefrom Bacillus stearothermophilus Skarzynski, T., Moody, P. C. E., Wonacott, A. J.: Structure of Holo-Glyceraldehyde-3-Phosphate Dehydrogenase from Bacillus Stearothermophilus at 1.8 Angstroms Resolution. J.Mol.Biol. 193 pp. 171 (1987) Picture source: SWISS-PROT

  22. a b Fe b a The Globin Gene Family • Globin genes code for the protein portion of hemoglobin • In adults, hemoglobin is made up of an iron containing heme molecule surrounded by 4 globin proteins: 2 a globins and 2 b globins • During development, different globin genes are expressed which alter the oxygen affinity of embryonic and fetal hemoglobin

  23. Haemoglobin Luisi, B., Shibayama, N.: Structure of Haemoglobin in the Deoxy Quaternary State with Ligand Bound at the Alpha Haems. J.Mol.Biol. 206 pp. 723 (1989) Picture source: SWISS-PROT

  24. The End

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