1. Fundamentals of Biochemistry
Fourth Edition
Donald Voet • Judith G. Voet • Charlotte W. Pratt
Chapter 6
Proteins: Three-Dimensional Structure
Copyright © 2013 by John Wiley & Sons, Inc. All rights reserved.

2. Chapter 6 Secondary Structure Key Concepts 6.1
• The planar character of the peptide group limits the conformational flexibility of the polypeptide chain. • The α helix and the β sheet allow the polypeptide chain to adopt favorable φ and ψ angles and to form hydrogen bonds. • Fibrous proteins contain long stretches of regular secondary structure, such as the coiled coils in α keratin and the triple helix in collagen. • Not all polypeptide segments form regular secondary structure such as α helices or β sheets.

3. Levels of Protein Structure

4. 1° Structure

5. 1° & 2° Structure

6. 1°, 2°, & 3° Structure

7. 1°, 2°, 3° & 4° Structure

8. Peptide Bonds Assume Trans Conformation

9. Resonance of Peptide Bond

10. Extended Conformation of Polypeptide

11. Torsion Angles of Polypeptide Backbone

12. Steric Interference of Adjacent Peptide Groups

13. Ramachandran Diagram

14. The α Helix

15. The α Helix: Space Filling Model Oxy-Myoglobin PDBid 1A6M

16. β Sheets

17. Antiparallel β Sheet

18. Parallel β Sheet

19. Pleating of β Sheet

20. β Sheet: Space Filling Model Concanavalin A PDBid 2CNA

21. Bovine Carboxypeptidase A Carboxypeptidase A PDBid 3CPA

23. Figure: UN
Title:
Intrachain and interchain disulfide bridges.
Caption:
Intrachain disulfide bridges bond together different parts of the same polypeptide molecule. Interchain disulfide bridges bond together different polypeptide molecules.

24. Figure: 22.7
Title:
Figure Disulfide bridges cross-linking portions of a peptide.
Caption:
Disulfide bridges contribute to the overall shape of the protein.

25. α-helix
β-sheet
Tertiary Structure

26. Figure: 22.12
Title:
Figure Stabilizing interactions involved in maintaining the tertiary structure of a protein.
Caption:
Tertiary structure is maintained by interactions between side chains of different amino acids within the same protein molecule.

27. Connecting Adjacent β Strands

28. A Coiled Coil

29. A Coiled Coil
Tropomyosin PDBid 1IC2

30. Higher Order Structure of α Keratin

31. Collagen: Triple Helix

32. Sequence Affects 2º Structure

33. Chapter 6 Tertiary Structure Key Concepts 6.2
• X-Ray crystallography and NMR spectroscopy are used to determine the positions of atoms in proteins. • Nonpolar residues tend to occur in the protein interior and polar residues on the exterior. • A protein’s tertiary structure consists of secondary structural elements that combine to form motifs and domains. • Over time, a protein’s structure is more highly conserved than its sequence. • Bioinformatics databases store macromolecular structure coordinates. Software makes it possible to visualize proteins and compare their structural features.

34. Oxy-Myoglobin and Concanavalin A PDBids 1A6M and 2CNA
Side Chain Location
Oxy-Myoglobin and Concanavalin A PDBids 1A6M and 2CNA

35. Side Chain Distribution in Cytochrome

36. Side Chain Distribution in Cytochrome

37. Side Chain Distribution in Cytochrome

38. Motifs: Supersecondary Structures

39. Protein Classification: α, β, or α/β
Human immunoglobulin fragment PDBid 7FAB
Dogfish lactate dehydrogenase PDBid 6LDH
Cytochrome b562 PDBid 256B

40. Protein Classification: α
Cytochrome b562 PDBid 256B

41. Protein Classification: β Human immunoglobulin fragment PDBid 7FAB

42. Protein Classification: α/β Dogfish lactate dehydrogenase PDBid 6LDH

43. Protein Topology: 8-Stranded β Barrels
Peptide-N4-(N-acetyl--D-glucosaminyl) asparagine amidase PDBid 1PNG
Human retinol binding protein PDBid 1RBP
Triose phosphate isomerase PDBid 1TIM

44. Protein Topology: 8-Stranded β Barrels
Human retinol binding protein PDBid 1RBP

45. Protein Topology: 8-Stranded β Barrels
Peptide-N4-(N-acetyl--D-glucosaminyl) asparagine amidase PDBid 1PNG

46. Protein Topology: 8-Stranded β Barrels
Triose phosphate isomerase PDBid 1TIM

47. 2-Domain Protein : GAPDH
Glyceraldehyde-3-phosphate dehydrogenase PDBid 1GD1

48. Structure Conserved More Than Sequence

49. Internet Bioinformatics Tools

50. Quaternary Structure & Symmetry
Chapter 6
Quaternary Structure & Symmetry
Key Concepts 6.3
• Some proteins contain multiple subunits, usually arranged symmetrically.

51. 4º Structure of Hemoglobin Deoxyhemoglobin PDBid 2DHB

52. Chapter 6 Protein Stability Key Concepts 6.4
• Protein stability depends primarily on hydrophobic effects and secondarily on electrostatic interactions. • A protein that has been denatured may undergo renaturation. • Protein structures are flexible and may include unfolded regions.

53. Hydrophobic & Hydrophilic Tendencies:
Hydropathy

54. Bovine Chymotrypsinogen
Hydropathy Plot:
Bovine Chymotrypsinogen

55. Ion Pairs in Hemoglobin

56. Metal Ion Stabilized Zinc Finger DNA-binding protein Zif268 PDBid 1ZAA

57. Chaotropic Agents Denature Proteins

58. Chapter 6 Protein Stability Checkpoint 6.4
• Describe the hydropathic index plot for a fibrous protein such as collagen or keratin. • Describe the forces that stabilize proteins, and rank their relative importance. • Summarize the results of Anfinsen’s experiment with RNase A. • Why would it be advantageous for a protein or a segment of a protein to lack defined secondary or tertiary structure?

59. Chapter 6 Protein Folding Key Concepts 6.5
• A folding protein follows a pathway from high energy and high entropy to low energy and low entropy. • Protein disulfide isomerase catalyzes disulfide bond formation. • A variety of molecular chaperones assist protein folding via an ATP-dependent bind-and-release mechanism. • Amyloid diseases result from protein misfolding. • The misfolded proteins form fibrils containing extensive β structure.

60. Hypothetical Protein Folding Pathway

61. Energy-Entropy Diagram: Protein Folding Funnel

62. Protein Disulfide Isomerase Catalyzes Disulfide Interchange

63. Protein Disulfide Isomerase Catalyzes Disulfide Interchange

64. Protein Disulfide Isomerase Catalyzes Disulfide Interchange

65. Box 6-4: Protein Structure Prediction & Protein Design
Hypothetical proteins PDBids 1WHZ and 2HH6

66. Protein Folding & Disease

67. Alzheimer’s Disease: Amyloid Plaques

68. Prion Rods