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1. Introduction
2. Overview
3. Limited proteolysis vs. degradation
4. Regulation of proteolytic activity (1)
5. Regulation of proteolytic activity (2)
6. Apoptotic pathway
7. Caspase structure (1)
8. Caspase structure (2)
9. Caspase structure - the active site
10. Caspase structure - zooming in the active site
11. Caspase zymogen activation
12. Monomer/dimer status of caspase zymogens
13. Initiator and executioner caspases
14. Natural caspase inhibitors
15. CrmA
16. Selectivity of CrmA
17. p35
18. Selectivity of p35
19. p35 docks into active site of caspases
20. CrmA and caspases active site
21. Viral "suicide" caspase inhibitors
22. IAPs - the endogenous caspase regulators
23. Human IAPs (BIRC 1-8)
24. Some other IAPs
25. Mouse IAPs knockout phenotypes
26. Multiple proposed IAP functions
27. The BIR domain (1)
28. The BIR domain (2)
29. IAPs as caspase inhibitors - XIAP, the paradigm
30. Domain organization of XIAP
31. Caspase 3/BIR2 complex
32. Structure of caspase 3/DEVD-CHO
33. Structure of the caspase 3/BIR2 complex
34. Inhibitor footprints and the role of the 381 loop
35. Caspase-3 bound state
36. Caspase-3 free state
37. Two site interaction hypothesis
38. BIR2 mechanism
39. Comparison of XIAP-BIR complexes
40. BIR3 mechanism
41. XIAP inhibition of caspases
42. Caspase activation vs. IAP derepression
43. The SMAC groove...competition of IBMs
44. IBMs
45. SMAC mechanism - caspase 9/BIR3
46. BIR domain topology
47. BIR2 domain comparisons - the SMAC groove
48. BIR2 domain comparisons - the N-terminal linker
49. BIR3 domain comparisons - the SMAC groove
50. BIR2 domain comparisons - the C-terminal helix
51. Variations in N-terminal linker or C-terminal helix
52. Human IAPs (BIRC 1-8)
53. What about the other 7 human IAPs?
54. Acknowledgements
55. Representative reviews

Topics Covered

• Apoptosis
• Proteolytic mechanisms
• Caspases
• Activation mechanisms
• Natural caspase inhibitors
• Viral inhibitors
• IAPs
• Inhibitory mechanisms
• IAP antagonists
• Theory of activating apoptosis by de-repression of caspase inhibition

Links

Series:

• Apoptosis

Categories:

• Cell Biology

Therapeutic Areas:

• Immunology & Inflammation

Talk Citation

Publication History

• Published on October 1, 2007

Financial Disclosures

• Prof. Guy Salvesen has not informed HSTalks of any commercial/financial relationship that it is appropriate to disclose.