Historical Landmarks in Our Understanding of Proteins

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Historical Landmarks in Our Understanding of
Proteins

• 1838 The name "protein" (from the Greek proteios,
  "primary") was suggested by Berzelius for the
  complex organic nitrogen-rich substance found in
  the cells of all animals and plants.
• 1819-1904 Most of the 20 common amino acids found
  in proteins were discovered.
• 1864 Hoppe-Seyler crystallized, and named, the
  protein hemoglobin.
• 1894 Fischer proposed a lock-and-key analogy for
  enzyme-substrate interactions.
• 1897 Buchner and Buchner showed that cell-free
  extracts of yeast can ferment sucrose to form
  carbon dioxide and ethanol, thereby laying the
  foundations of enzymology.
• 1926 Svedberg developed the first analytical
  ultracentrifuge and used it to estimate the
  correct molecular weight of hemoglobin.
• 1933 Tiselius introduced electrophoresis for
  separating proteins in solution.
• 1942 Martin and Synge developed chromatography, a
  technique now widely used to separate proteins.
• 1951 Pauling and Corey proposed the structure of
  a helical conformation of a chain of L-amino
  acids -- the alpha helix -- and the structure of
  the beta sheet, both of which were later found
  in many proteins.
• 1955 Sanger completed the analysis of the amino
  acid sequence of insulin, the first protein to
  have its amino acid sequence determined.
• 1956 Ingram produced the first protein
  fingerprints, showing that the difference between
  sickle- cell hemoglobin and normal hemoglobin is
  due to a change in a single amino acid.
• 1963 Monod, Jacob, and Changeux recognized that
  many enzymes are regulated through allosteric
  changes in their conformation.

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Number Size Distribution of Cellular Proteins
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Size Shape Comparisons of Proteins
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Protein Structure and Function

• Protein Structure
• Primary structure - amino acid sequence.
• Secondary structure - formation of a helices and
  b sheets.
• Tertiary structure - the three-dimensional
  conformation of a polypeptide chain.
• Quaternary structure - formation of a protein
  molecule as a complex of more than one
  polypeptide chain.

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Protein Structure and Function

• Protein Function
• Enzymes - proteases, synthetases, polymerases,
  kinases
• Structural - extracellular collagen, elastin
  intracellular tubulin, actin, a-keratin
• Transport - serum albumin, hemoglobin,
  transferrin
• Motor - myosin, kinesin, dynein
• Storage - ferritin, ovalbumin, calmodulin
• Signaling - insulin, nerve growth factor,
  integrins
• Receptor - acetylcholine receptor, insulin
  receptor, EGF receptor
• Gene regulatory - lactose repressor, homeodomain
  proteins
• Special purpose - green fluorescent protein, glue
  proteins

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Protein Structure and Function

• Protein Structure
• Primary structure - amino acid sequence.
• Secondary structure - formation of a helices and
  b sheets.
• Tertiary structure - the three-dimensional
  conformation of a polypeptide chain.
• Quaternary structure - formation of a protein
  molecule as a complex of more than one
  polypeptide chain.

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Amino Acids
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Codon Usage Table
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Protein Folding
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Protein Denaturation Refolding
Protein confirmation is determined solely by its
amino acid sequence
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Protein Structure and Function

• Protein Structure
• Primary structure - amino acid sequence.
• Secondary structure - formation of a helices and
  b sheets.
• Tertiary structure - the three-dimensional
  conformation of a polypeptide chain.
• Quaternary structure - formation of a protein
  molecule as a complex of more than one
  polypeptide chain.

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a helix Secondary Structure
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b sheet Secondary Structure
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Noncovalent Bonds
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Noncovalent Bonds
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Hydrogen Bonds in Proteins
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Noncovalent Bonds
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Noncovalent Bonds
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Noncovalent Bonds
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Noncovalent Bonds
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b sheet Secondary Structure
Antiparallel b sheet
Parallel b sheet
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a helix Interactions with Phospholipids
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Protein Structure and Function

• Protein Structure
• Primary structure - amino acid sequence.
• Secondary structure - formation of a helices and
  b sheets.
• Tertiary structure - the three-dimensional
  conformation of a polypeptide chain.
• Quaternary structure - formation of a protein
  molecule as a complex of more than one
  polypeptide chain.

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Tertiary Structure
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Tertiary Structure
Cytochrome b Lactate dehydrogenase IgG
light chain
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Structural Importance in Protein Function
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Coiled-coiled Structure of Multiple a helices

• A single a helix with amino acids a and d being
  nonpolar.
• B two a helices wrap around each other with one
  nonpolar side chain interacting with the
  nonpolar side chain of the other. The
  hydrophilic side chains are exposed to the
  aqueous environment.
• C atomic structure of a coiled-coil showing the
  nonpolar interactions in red

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Protein Structure and Function

• Protein Structure
• Primary structure - amino acid sequence.
• Secondary structure - formation of a helices and
  b sheets.
• Tertiary structure - the three-dimensional
  conformation of a polypeptide chain.
• Quaternary structure - formation of a protein
  molecule as a complex of more than one
  polypeptide chain.

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Quaternary Structure
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Quaternary Structure
Hemoglobin
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Protein - Protein Interactions

• A protein with just one binding site can form a
  dimer with an identical protein.
• Identical proteins with two different binding
  sites can form a long helical filament.
• If the two binding sites are located
  appropriately to each other, the protein subunits
  can form a closed ring instead of a helix.

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Collagen and Elastin
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Disulfide bonds