Historical Landmarks in Our Understanding of Proteins

1. 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.

2. Number & Size Distribution of Cellular Proteins

3. Size & Shape Comparisons of Proteins

4. 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.

5. 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

6. 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.

7. Amino Acids

8. Codon Usage Table

9. Protein Folding

10. Protein Denaturation & Refolding Protein confirmation is determined solely by its amino acid sequence

11. 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.

12. a helix Secondary Structure

13. b sheet Secondary Structure

14. Noncovalent Bonds

15. Noncovalent Bonds

16. Hydrogen Bonds in Proteins

17. Noncovalent Bonds

18. Noncovalent Bonds

19. Noncovalent Bonds

20. Noncovalent Bonds

21. b sheet Secondary Structure Antiparallel b sheet Parallel b sheet

22. a helix Interactions with Phospholipids

23. 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.

24. Tertiary Structure

25. Tertiary Structure Cytochrome b Lactate dehydrogenase IgG light chain

26. Structural Importance in Protein Function

27. 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

28. 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.

29. Quaternary Structure

30. Quaternary Structure Hemoglobin

31. 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.

32. Collagen and Elastin

33. Disulfide bonds