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1. Introduction
2. Lecture topics
3. The ubiquitin-proteasome pathway
4. Ubiquitin forms polymers with different linkages
5. The proteasome: how is it constructed in vivo?
6. Structure of the 26S proteasome (1)
7. Structure of the 26S proteasome (2)
8. Specific placement of 14 different CP subunits
9. Stochastic self-assembly or chaperone-assisted
10. The beta5 subunit is synthesized in precursor form
11. The beta5 propeptide functions in trans
12. Autocatalytic processing
13. Overproduced beta7 subunit allows a bypass
14. The beta7 C-tail is required for bypass
15. High-copy beta7 drives beta-ring completion
16. Model for 20S proteasome assembly
17. Yeast Pba3 and Pba4
18. Native PAGE analysis of yeast cell extracts
19. Pba3/4 is required for proteasome assembly
20. Pba3/4 and alpha3 subunit incorporation
21. Deletion of alpha3
22. Pba3/4 loss leads to 20S proteasome remodeling
23. Conclusion
24. alpha4-alpha4 confer a selective advantage
25. Accumulation of altered 20S proteasomes
26. Pba3/4 directs formation of a 20S proteasome
27. Dedicated chaperones for the proteasome
28. NAS2 identified as an extragenic suppressor
29. Loss of Nas2 enhances the proteolytic defect
30. Loss of Nas2 has a very weak effect on RP
31. Nas2 co-purifies in a stoichiometric complex
32. Rpt4-Rpt5 can assembly into 26S proteasomes
33. Purification and LC-MS/MS of novel subcomplexes
34. Multiple assembly chaperones (1)
35. Synthetic genetic interactions between deletions
36. Striking RP base assembly
37. Multiple assembly chaperones (2)
38. Is there a specific proteasomal RP pathway?
39. Archaeal PAN ATPase homohexamer as model
40. The PAN homohexamer is a trimer of dimers
41. Structural features of PAN ATPase interfaces
42. Eukaryotic ATPase heterohex. arrangement (1)
43. Sites chosen for disulfide engineering
44. The Rpt4 and Rpt5 ATPases interact directly
45. Eukaryotic ATPase heterohex. arrangement (2)
46. RP assembly model revisited
47. Revision of assembly model
48. Assembly chaperones for the proteasome
49. Acknowledgements

Topics Covered

• The ubiquitin-proteasome system
• Proteasome composition and structure
• 20S proteasome core particle assembly
• 19S regulatory particle assembly

Links

Series:

• Protein Homeostasis

Categories:

• Biochemistry
• Cell Biology

Talk Citation

Publication History

• Published on February 2, 2012

Financial Disclosures

• Prof. Mark Hochstrasser, Consultant: Millennium Pharmaceuticals, Inc. (ad hoc consultant)