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Proteins:  structure & function Based on a presentation by Timothy G. Standish
The Genetic Code S E C O N D  B A S E A GGU GGC GGA GGG Gly* AGU AGC AGA AGG Arg G CGU CGC CGA CGG Arg G UGU UGC UGA UGG C...
Different Amino Acid Classes Polar Basic Acid ? Acid Amine OH O H H 2 N C C R Generic Non-polar C C C OH H H O H + N H H 2...
Non-Polar Amino Acids OH O H H 2 N C C H Glycine Leucine OH O H H 2 N C C H 3 C CH 3 H C H H C Methionine OH O H H 2 N C C...
Polar Amino Acids Cysteine C C C OH H H O HS H H 2 N Serine OH O H H 2 N C C HO CH 3 H C Threonine OH O H H 2 N C C H H C ...
Acidic Amino Acids Aspartic  acid H H 2 N C C H H O OH O C OH C Glutamic acid H H 2 N C C H H O OH O C OH C C H H
Basic Amino Acids Histidine C C C OH H H O H + N H H 2 N C NH C C Lysine OH O H H 2 N C C + H 3 N H H C H H C C H H H H C ...
Levels Of Protein Organization <ul><li>Primary Structure -  The sequence of amino acids in the protein </li></ul><ul><li>S...
Levels Of Protein Organization Primary Structure Met- Gly -Ala-Pro- His -Ile- Asp - Glu -Met- Ser - Thr -...
Glyceraldehyde-3-Phosphate Dehydrogenase Primary Structure <ul><li>The  Mycoplasma genitalium  G-3P dehydrogenase protein ...
Protein Secondary Structure <ul><li>The peptide backbone of DNA has areas of positive charge and negative charge </li></ul...
Protein Secondary  Structure:    Helix + - C O OH C N H H H C HO H C H O C N H H H C H H C H N C O C H N O C C O C H N C ...
Protein Secondary  Structure:    Helix + - C O OH C N H H H C HO H C H O C N H H H C H H C H N C O C H N O C C O C H N C ...
Protein Secondary Structure:   Helix R groups stick out from the    helix influencing higher levels of protein organizat...
Protein Secondary Structure:   Helix
Yeast Cytochrome C Oxidase Subunit IV Leader <ul><li>This leader sequence probably forms an    helix </li></ul><ul><li>Th...
Protein Secondary Structure:   Pleated Sheet N H C O C H C C N O N H C O C H C C N O N H C O C H C C N O N H C O C H C C ...
Protein Secondary Structure:   Pleated Sheet N H C O C H C C N O N H C O C H C C N O N H C O C H C C N O N H C O C H C C ...
Protein Secondary Structure:   pleated sheet
Protein Secondary Structure: α  helices and    pleated sheets
Levels Of Protein Organization Tertiary Structure <ul><li>Tertiary structure results from the folding of    helices ,   ...
G-3-P Dehydrogenase Tertiary Structure Picture source: SWISS-PROT
Levels Of Protein Organization Quaternary Structure <ul><li>Quaternary structure results from the interaction of independe...
G-3-P Dehydrogenase from Bacillus stearothermophilus Skarzynski, T., Moody, P. C. E., Wonacott, A. J.: Structure of Holo-G...
The Globin Gene Family <ul><li>In adults, hemoglobin is made up of an iron containing heme molecule surrounded by 4 globin...
Haemoglobin <ul><li>Luisi, B., Shibayama, N.: Structure of Haemoglobin in the Deoxy Quaternary State with Ligand Bound at ...
 
Protein denaturation <ul><li>Change in the tertiary/quartenary structure –breakins of bonds </li></ul><ul><li>Denaturated ...
Protein denaturation
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Protein Structure & Function

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Transcript of "Protein Structure & Function"

  1. 1. Proteins: structure & function Based on a presentation by Timothy G. Standish
  2. 2. The Genetic Code S E C O N D B A S E A GGU GGC GGA GGG Gly* AGU AGC AGA AGG Arg G CGU CGC CGA CGG Arg G UGU UGC UGA UGG C GAU GAC GAA GAG AAU AAC AAA AAG Glu CAU CAC CAA CAG A UAU UAC UAA UAG Stop Tyr GUU GUC GUA GUG Val AUU AUC AUA AUG start Ile CUU CUC CUA CUG Leu U UUU UUC UUA UUG Leu Phe Met/ GCU GCC GCA GCG Ala ACU ACC ACA ACG Thr CCU CCC CCA CCG Pro C UCU UCC UCA UCG Ser U C A G U U C A G U C A G U C A G Gln † His Trp Cys T H I R D B A S E F I R S T B A S E Asp Lys Asn † Stop Ser Neutral Non-polar Polar Basic Acidic † Have amine groups * Listed as non-polar by some texts
  3. 3. Different Amino Acid Classes Polar Basic Acid ? Acid Amine OH O H H 2 N C C R Generic Non-polar C C C OH H H O H + N H H 2 N C NH C C Histidine H H 2 N C C H H O OH O C OH C Aspartic acid C C C OH H H O HS H H 2 N Cysteine OH H H O H H H 2 N C C C Alanine
  4. 4. Non-Polar Amino Acids OH O H H 2 N C C H Glycine Leucine OH O H H 2 N C C H 3 C CH 3 H C H H C Methionine OH O H H 2 N C C H 3 C H H C H H C S Alanine OH H H O H H H 2 N C C C Valine OH O H H 2 N C C H 3 C CH 3 H C Phenylalanine OH H H O H H 2 N C C C Tryptophan OH O H H 2 N C C NH H C H Isoleucine OH O H H 2 N C C H 3 C H H C H H 3 C C Proline OH O H H 2 N + C C H 2 C CH 2 H 2 C
  5. 5. Polar Amino Acids Cysteine C C C OH H H O HS H H 2 N Serine OH O H H 2 N C C HO CH 3 H C Threonine OH O H H 2 N C C H H C OH H C H Tyrosine HO H H O H H 2 N C C C OH Asparagine H H 2 N C C H H O OH O C NH 2 C Glutamine H H 2 N C C H H O OH O C NH 2 C C H H
  6. 6. Acidic Amino Acids Aspartic acid H H 2 N C C H H O OH O C OH C Glutamic acid H H 2 N C C H H O OH O C OH C C H H
  7. 7. Basic Amino Acids Histidine C C C OH H H O H + N H H 2 N C NH C C Lysine OH O H H 2 N C C + H 3 N H H C H H C C H H H H C Arginine OH O H H 2 N C C H H C H H C C H H H N + H 2 N NH 2 C
  8. 8. Levels Of Protein Organization <ul><li>Primary Structure - The sequence of amino acids in the protein </li></ul><ul><li>Secondary Structure - The formation of  helices and  pleated sheets due to hydrogen bonding between the peptide backbone </li></ul><ul><li>Tertiary Structure - Folding of helices and sheets influenced by R groups </li></ul><ul><li>Quaternary Structure - The association of more than one polypeptide into a protein complex influenced by R groups </li></ul>
  9. 9. Levels Of Protein Organization Primary Structure Met- Gly -Ala-Pro- His -Ile- Asp - Glu -Met- Ser - Thr -...
  10. 10. Glyceraldehyde-3-Phosphate Dehydrogenase Primary Structure <ul><li>The Mycoplasma genitalium G-3P dehydrogenase protein sequence: </li></ul><ul><li>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 </li></ul>
  11. 11. Protein Secondary Structure <ul><li>The peptide backbone of DNA has areas of positive charge and negative charge </li></ul><ul><li>These areas can interact with one another to form hydrogen bonds </li></ul><ul><li>The result of these hydrogen bonds are two types of structures: </li></ul><ul><ul><li> helices </li></ul></ul><ul><ul><li> pleated sheets </li></ul></ul>
  12. 12. Protein Secondary Structure:  Helix + - C O OH C N H H H C HO H C H O C N H H H C H H C H N C O C H N O C C O C H N C H N C O C O C O C O C H N H N C H N
  13. 13. Protein Secondary Structure:  Helix + - C O OH C N H H H C HO H C H O C N H H H C H H C H N C O C H N O C C O C H N C H N C O C O C O C O C H N H N C H N
  14. 14. Protein Secondary Structure:  Helix R groups stick out from the  helix influencing higher levels of protein organization R R R R R R R R R R R R R R
  15. 15. Protein Secondary Structure:  Helix
  16. 16. Yeast Cytochrome C Oxidase Subunit IV Leader <ul><li>This leader sequence probably forms an  helix </li></ul><ul><li>This would localize specific classes of amino acids in specific parts of the helix </li></ul><ul><li>There are about 3.6 amino acids per turn of the helix with a rise of 0.54 nm per turn </li></ul>ML S L R QS I R FF K PA T R T L CSS R Y LL Neutral Non-polar Polar Basic Acidic R Y P L T C S R L S T I K P R F A F M R Q L L S S First 12 residues are sufficient for transport to the mitochondria
  17. 17. Protein Secondary Structure:  Pleated Sheet N H C O C H C C N O N H C O C H C C N O N H C O C H C C N O N H C O C H C C N O N H C O C H C C N O N H C O C H C C N O N H C O C H C C N O N H C O C H C C N O
  18. 18. Protein Secondary Structure:  Pleated Sheet N H C O C H C C N O N H C O C H C C N O N H C O C H C C N O N H C O C H C C N O N H C O C H C C N O N H C O C H C C N O N H C O C H C C N O N H C O C H C C N O N H C O C H C C N O N H C O C H C C N O N H C O C H C C N O N H C O C H C C N O
  19. 19. Protein Secondary Structure:  pleated sheet
  20. 20. Protein Secondary Structure: α helices and  pleated sheets
  21. 21. Levels Of Protein Organization Tertiary Structure <ul><li>Tertiary structure results from the folding of  helices ,  pleated sheets and other areas with other/no secondary structure </li></ul><ul><li>Factors influencing tertiary structure include: </li></ul><ul><ul><li>Hydrophobic/hydrophilic interactions </li></ul></ul><ul><ul><li>Hydrogen bonding </li></ul></ul><ul><ul><li>Disulfide linkages </li></ul></ul><ul><ul><li>Folding by chaperone proteins </li></ul></ul>
  22. 22. G-3-P Dehydrogenase Tertiary Structure Picture source: SWISS-PROT
  23. 23. Levels Of Protein Organization Quaternary Structure <ul><li>Quaternary structure results from the interaction of independent polypeptide chains </li></ul><ul><li>Factors influencing quaternary structure include: </li></ul><ul><ul><li>Hydrophobic/hydrophilic interactions </li></ul></ul><ul><ul><li>Hydrogen bonding </li></ul></ul><ul><ul><li>The shape and charge distribution on associating polypeptides </li></ul></ul>
  24. 24. G-3-P Dehydrogenase from 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
  25. 25. The Globin Gene Family <ul><li>In adults, hemoglobin is made up of an iron containing heme molecule surrounded by 4 globin polypeptide chains: 2  globins and 2  globins </li></ul><ul><li>During development, different globin polypeptides are synthesized which alter the oxygen affinity of embryonic and fetal hemoglobin </li></ul>Fe    
  26. 26. Haemoglobin <ul><li>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) </li></ul>Picture source: SWISS-PROT
  27. 28. Protein denaturation <ul><li>Change in the tertiary/quartenary structure –breakins of bonds </li></ul><ul><li>Denaturated proteins cannot play their role in cells </li></ul><ul><li>Denaturation is often irreversible (eg. fried egg yolk cannot be ‘unfried’) </li></ul><ul><li>Denaturating agents include acids, bases, detergents, heavy metals </li></ul>
  28. 29. Protein denaturation
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