5. Operone lac

7. Principles of protein structure and function Function is derived from structure Structure is derived from amino acid sequence Different activities and shapes of proteins due to different amino acid sequences

8. Four levels of protein structure Primary: amino acid sequence

9. Four levels of protein structure Primary: amino acid sequence Secondary: regular, repeated coiling and folding of polypeptide backbone

10. Four levels of protein structure Primary: amino acid sequence Secondary: regular, repeated coiling and folding of polypeptide backbone Tertiary: complete three-dimensional structure Quaternary: arrangement of subunits (in multisubunit protein)

11. Secondary structure Regular, repeated coiling and folding of polypeptide backbone Due to hydrogen bonding Two patterns –  (alpha) helix –  (beta) sheet

12. Tertiary Complete three-dimensional structure Due to weak interactions between side (R) groups as well as covalent disulfide bonds Weak interactions Hydrogen bonds Electrostatic interactions (ionic bonds) Hydrophobic interactions Van der Waals interactions

13. Tertiary structure formed through side chain interactions

15. Hydrophobic interactions

16. Tertiary Complete three-dimensional structure Composed of: –Motifs: specific combinations of secondary structural elements –Domains: structurally independent units

17. Motifs specific combinations of secondary structural elements

18. Domains Structurally independent units Two different binding domains to bind two different molecules

19. Tertiary Complete three-dimensional structure Native conformation: functional structure Most stable conformation

20. Tertiary Fibrous Proteins = extended filaments or Globular proteins = compact folded structure

21. Protein Folding Forming polypeptide chain requires energy and information (template)

22. Protein Folding Forming polypeptide chain requires energy and information (template) Forming native conformation requires NO additional energy or information (SELF ASSEMBLY)

23. Protein folding Amino acid sequence contains all information necessary for folding into a specific three- dimensional structure

24. Protein Folding

25. Many proteins fold by Assisted Self Assembly Correct assembly (native conformation) requires assistance by CHAPERONES

26. Protein unfolding = Denaturation Loss of structure and function –Heat –Extreme pH –Detergents –Urea

27. Protein unfolding = Denaturation Why do these conditions cause loss of structure and function? –Heat –Extreme pH –Detergents –Urea

28. Tertiary Complete three-dimensional structure Due to weak interactions between side (R) groups as well as covalent disulfide bonds

29. Lysozyme

31. Tertiary: complete three-dimensional structure Quaternary: arrangement of subunits (in multisubunit protein)

32. Folding dell’emoglobina Ribbon diagram

33. Hemoglobin

34. Quaternary structure Held together by weak interactions between side (R/functional) groups as well as covalent disulfide bonds

35. Structure-function relationship Function is derived from structure Structure is derived from sequence

36. Sickle-cell disease Normal red blood cells Sickle shaped red blood cells Due to single amino acid change in hemoglobin = protein carries oxygen in red blood cells

37. Sickle-cell disease

38. Single specific amino acid change causes change in protein structure and solubility Results in change in cell shape Causes cells to clog blood vessels

39. Structure-function relationship Function is derived from structure Structure is derived from sequence

40. Molecules with similar shapes can interact in similar ways. –For example, morphine, heroin, and other opiate drugs are similar enough in shape that they can bind to the same receptors as natural signal molecules, called endorphins. –Binding to the receptors produces euphoria and relieves pain. Copyright © 2002 Pearson Education, Inc., publishing as Benjamin Cummings Fig. 2.19

41. Structure-function relationship Function is derived from structure Structure is derived from sequence ›Similar sequences have similar functions

42. Structure-function relationship Function is derived from structure Structure is derived from sequence ›Similar sequences have similar functions ›Similar function often implies evolutionary relatedness (homology) »Sequence similarity suggests common evolutionary origin

43. Homologous proteins Similar sequence Similar structure Similar function Evolved from common ancestor Belong to protein family

44. Proteins Protein modification and degradation 1. Covalent chemical modification 2. Proteolytic processing and protein splicing 3. Proteolytic degradation

45. Reading and questions Chapter 3 Questions 3-1, 3-2, 3-8, 3-11a, 3-15a -15d -15e, 3-16