Protein Structure

1. Protein Structure September 7, 12 2006

2. Basics of Protein Structure • Primary structure: sequence • Secondary structure: • α-helix, -sheet, -strand, loop • Supersecondary structure, motifs • Tertiary structure: • folding into functional domains with ordered structure composed of secondary structure elements • Quaternary structure • Complexes of monomers to form active structures

3. Amino acid

4. 20 amino acids - the building blocks

5. Amino acid categories • Aliphatic • Valine, Alanine, Leucine and Isoleucine • Aromatic • Phenylalanine, Tyrosine and Tryptophan • Charged • Aspartic, Glutamic, Histidine, Lysine, Arginine • Polar • Serine, Threonine, Cysteine, Methionine, Asparagine, Glutamine • Odd couple • Glycine, Proline

6. Aliphatic residues

7. Aromatic Residues

8. Charged Residues • Side-chains are charged under physiological conditions • Acid are negatively charged • Basic are positively charged

9. Polar Residues

10. The Odd Couple

11. Peptide-bond formation

12. w Backbone torsion angles • f phi y psi • omega 180° trans 0° cis

13. Ramachandran Plot

14. Other chemical bonds • Disulfide bonds or bridges • Formed by oxidation of thiol groups of two cysteines • Form a bond about 2Å in length. • Predominant feature in many small proteins • H-bonds not truly covalent • Dipolar attraction between O and H • Complex geometry wrt distances and angles

15. Side Chain Conformation

16. Side Chain Torsion Angles The side chain torsion angles are named c1(chi1), c2(chi2), c3 (chi3), etc., as shown below for lysine.

18. Hydrophilic or hydrophobic…? • Virtually all soluble proteins feature a hydrophobic core surrounded by a hydrophilic surface • Peptide backbone is inherently polar • Neutralize potential H-donors & acceptors using ordered secondary structure

19. Alpha helix • H-bonds between N-H and C=O groups in polypeptide backbone • Compact structure • 3.6 residues • Pitch: 5.6Å/turn • Rise: 1.5Å/residue • Polar/hydrophilic residues on 1 face with nonpolar or hydrophobic residues on other face

20. Secondary Structure: -helix • 3.6 residues / turn • Axial dipole moment • Not Proline & Glycine • Protein surfaces

22. Beta-sheet • Extended structure • Side-chains project alternately up or down • Amphipathic is solvent exposed • polar residues on one side and non-polar on other side

23. Secondary Structure: -sheets

24. Secondary Structure: -sheets • Parallel or antiparallel • Alternating side-chains • No mixing • Loops often have polar amino acids

25. Parallel -sheets:

26. Antiparallel -sheets:

27. Silk fibroin

28. Supersecondary structures • Also called motifs • Simple combinations of secondary structures

29. -hairpins

30. Two-residue -hairpins

31. Three-residue -hairpins

32. -meander

33. corners are observed to have a right-handed twist when viewed from the concave side

34. Helix hairpins

35. The  corner

36. EF hand

37.  motifs

38. Greek Key Motif

39. Tertiary Structure • Combinations of motifs to form domains • Three main classes • All alpha • Alpha/beta • All beta

40. Alpha Domain Structures • Four helix bundle • Globin fold

42. Myohemeyrthrin

43. Cytochrome b452

44. Ferritin

45. Globins

46. Packing of helices

48. Alpha/beta • TIM barrel • Rossmann fold • Horseshoe fold

49. TIM Barrel

50. Horseshoe Fold