1. 3 D Structure of Immunoglobulins
Hugh B. Fackrell
Filename:Kuby05b7.ppt

2. Performance Objectives
Assigned Reading
Content Outline
Performance Objectives
Key terms
Key Concepts
Short Answer Questions

3. ASSIGNED READING
Chapter pp

4. Antibody structure Special antibodies to study structure
Myeloma proteins
Bence Jones Proteins
Monoclonal Antibodies
3D structure of antibodies
Binding site
Variability in structure

5. Angels & Devils

6. EM of IgA

7. Antibody flexibility

8. Antibody: Space filling model

9. Mulptiple Myeloma Disease Symptoms Detection Plasmocytoma
Cancer of antibody producing cell
Symptoms
recurrent infections, anaemia, fractures, pain, bone lesions
Detection
Electrophoresis, X-rays, blood smear

10. IgG Crystal

11. Myeloma Induction

12. Bence Jones Protein Homogenous light chains
In urine of myeloma patients
Easily purified
Insoluble at oC
Soluble at 80 oC

13. Monoclonal Antibodies
Add information here

14. Antibody model

15. Problems with flexibility
Difficult to determine entire structure
Hinge flexibility
Fragment
Study Fragment
Assemble composite

16. Hinge Prolines

17. IgG: Enzyme hydrolysis

18. Bence Jones Light chains
Simplest fragments to isolate
Easily crystallized
Mimics Fab

19. Bence Jones Monomer

20. Bence Jones Dimer

21. Immunoglobulin fold Signature structure common to all immunoglobulins
2 beta sheets
held by disulfide bond
Variations in detailed structure set specificity

22. Ig Fold: Variable domains

23. Ig fold: Constant domains

24. Antigen Binding Site

25. Structure of IgG

26. Ig Fold: hypervariable regions

27. Vitamin K bound to IgG

28. Antigen binding to Antibody

29. Antibody Strucutre: Internal motion

30. Antibody Structure: Internal movement

31. Antigen in Antibody

32. Hypervariable Regions
Discovery
KW plots
Light chains
Heavy chains
CDR vs HVR

33. Kabat & Wu Plots Why Results
demonstrate details of variability of protein sequence of similar proteins
Results
Variability = 1.0 >> no variation
Variability = 400 >> 20 different AA
Number different amino acids
Variability =
Frequency of most common AA

34. HV: light chains

35. KW plot heavy chains

36. HV:IgG

37. KW Heavy chains CDR

38. KW Light chains CDR

39. Ig Superfamily

40. Isotypes Allotypes Idiotypes

41. Allosera Production

42. Isotypes, Allotype Idiotype

43. The End

44. Performance Objectives
Key terms, concepts
short answers

45. SHORT ANSWER QUESTIONS