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.

Number & Size Distribution of Cellular Proteins

Size & Shape Comparisons of Proteins

Protein Structure and Function• Protein Structure

– Primary structure - amino acid sequence.

– Secondary structure - formation of helices and 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.

Protein Structure and Function• Protein Function

– Enzymes - proteases, synthetases, polymerases, kinases

– Structural - extracellular collagen, elastin intracellular tubulin, actin, -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

Protein Structure and Function• Protein Structure

– Primary structure - amino acid sequence.

– Secondary structure - formation of helices and 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.

Amino Acids

Codon Usage Table

Protein Folding

Protein Denaturation & Refolding

Protein confirmation is determined solely by its amino acid sequence

Protein Structure and Function• Protein Structure

– Primary structure - amino acid sequence.

– Secondary structure - formation of helices and 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.

helix Secondary Structure

sheet Secondary Structure

Noncovalent Bonds

Noncovalent Bonds

Hydrogen Bonds in Proteins

Noncovalent Bonds

Noncovalent Bonds

Noncovalent Bonds

Noncovalent Bonds

sheet Secondary Structure

Antiparallel sheet

Parallel sheet

helix Interactions with Phospholipids

Protein Structure and Function• Protein Structure

– Primary structure - amino acid sequence.

– Secondary structure - formation of helices and 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.

Tertiary Structure

Tertiary Structure

Cytochrome b Lactate dehydrogenase IgG light chain

Structural Importance in Protein Function

Coiled-coiled Structure of Multiple helices

• A single helix with amino acids a and d being nonpolar.

• B two 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

Protein Structure and Function• Protein Structure

– Primary structure - amino acid sequence.

– Secondary structure - formation of helices and 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.

Quaternary Structure

Quaternary Structure

Hemoglobin

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.

Collagen and Elastin

Disulfide bonds