Handout 4 - MCB 252 Cell Biology, Spring 2008 Handout 04...

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MCB 252 Cell Biology, Spring 2008 Handout 04 New Questions • How is a poly-ubiquitinated protein degraded? • How does a protein enter the nucleus? More generally,how is the nucleo-cytoplasmic trafficking regulated? • How is a protein poly-ubiquitinated?
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MCB 252 Cell Biology, Spring 2008 Handout 04 • How is a poly-ubiquitinated protein degraded? An oligo-ubiquitin chain marks the target protein for destruction without affecting the inherent stability of the protein. In the absence of the destruction apparatus, the protein bearing the signal is stable.
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MCB 252 Cell Biology, Spring 2008 Handout 04 • How is a poly-ubiquitinated protein degraded? The 26S proteasome is the machinery that specifically degrades poly-ubiquitinated proteins. It is a multi-subunit protease. It is very abundant (~1% of the cellular proteins). It is present in both the cytoplasm and the nucleus. Its activity is ATP dependent.
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MCB 252 Cell Biology, Spring 2008 Handout 04 The 26S proteasome • How is a poly-ubiquitinated protein degraded? regulatory cap regulatory cap core particle
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MCB 252 Cell Biology, Spring 2008 Handout 04 How is a poly-ubiquitinated protein degraded? EM of the 26S proteasome : can be fed in either direction. In the core particle chamber, of all the subunits in core chamber, Beta 1- cleaves near hydrophobic residues. Denature Protein in 20S
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MCB 252 Cell Biology, Spring 2008 Handout 04 1 α 1 α 7 α 6 α 5 α 4 α 2 α 3 α 2 α 6 α 7 α ß1 ß1 ß2 ß2 ß7 ß6 ß6 ß7 5 nm 15 nm 11 nm The 20S core particle • How is a poly-ubiquitinated protein degraded?
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MCB 252 Cell Biology, Spring 2008 Handout 04 ß α α ß Catalytic chamber Ante chambers • How is a poly-ubiquitinated protein degraded?
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MCB 252 Cell Biology, Spring 2008 Handout 04 How is a poly-ubiquitinated protein degraded?
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Handout 4 - MCB 252 Cell Biology, Spring 2008 Handout 04...

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