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Printable Handouts
Navigable Slide Index
- Introduction
- Lecture topics
- The ubiquitin-proteasome pathway
- Ubiquitin forms polymers with different linkages
- The proteasome: how is it constructed in vivo?
- Structure of the 26S proteasome (1)
- Structure of the 26S proteasome (2)
- Specific placement of 14 different CP subunits
- Stochastic self-assembly or chaperone-assisted
- The beta5 subunit is synthesized in precursor form
- The beta5 propeptide functions in trans
- Autocatalytic processing
- Overproduced beta7 subunit allows a bypass
- The beta7 C-tail is required for bypass
- High-copy beta7 drives beta-ring completion
- Model for 20S proteasome assembly
- Yeast Pba3 and Pba4
- Native PAGE analysis of yeast cell extracts
- Pba3/4 is required for proteasome assembly
- Pba3/4 and alpha3 subunit incorporation
- Deletion of alpha3
- Pba3/4 loss leads to 20S proteasome remodeling
- Conclusion
- alpha4-alpha4 confer a selective advantage
- Accumulation of altered 20S proteasomes
- Pba3/4 directs formation of a 20S proteasome
- Dedicated chaperones for the proteasome
- NAS2 identified as an extragenic suppressor
- Loss of Nas2 enhances the proteolytic defect
- Loss of Nas2 has a very weak effect on RP
- Nas2 co-purifies in a stoichiometric complex
- Rpt4-Rpt5 can assembly into 26S proteasomes
- Purification and LC-MS/MS of novel subcomplexes
- Multiple assembly chaperones (1)
- Synthetic genetic interactions between deletions
- Striking RP base assembly
- Multiple assembly chaperones (2)
- Is there a specific proteasomal RP pathway?
- Archaeal PAN ATPase homohexamer as model
- The PAN homohexamer is a trimer of dimers
- Structural features of PAN ATPase interfaces
- Eukaryotic ATPase heterohex. arrangement (1)
- Sites chosen for disulfide engineering
- The Rpt4 and Rpt5 ATPases interact directly
- Eukaryotic ATPase heterohex. arrangement (2)
- RP assembly model revisited
- Revision of assembly model
- Assembly chaperones for the proteasome
- Acknowledgements
Topics Covered
- The ubiquitin-proteasome system
- Proteasome composition and structure
- 20S proteasome core particle assembly
- 19S regulatory particle assembly
Talk Citation
Hochstrasser, M. (2012, February 2). Biogenesis of the eukaryotic proteasome [Video file]. In The Biomedical & Life Sciences Collection, Henry Stewart Talks. Retrieved January 24, 2021, from https://hstalks.com/bs/2215/.Publication History
Financial Disclosures
- Prof. Mark Hochstrasser, Consultant: Millennium Pharmaceuticals, Inc. (ad hoc consultant)
Biogenesis of the eukaryotic proteasome
Published on February 2, 2012
64 min