Lecture 4 "Chaperone-mediated protein fate"

• tag that marks protein for destruction by proteasome

1. Ub activation

   uibiquitinin is activated by the E1 ibiquitinn-activatng enyzme

2. Conjugation

   activtaed ubiquitinin is transferred from E1 to an E2 ubiquitinin-conjugating enzyme

3. ligation

   ligase brings E2 and the target protein together and transfers biquitinin to the substrate

4. more ubiquitinin can be attached to the chain, which is send to the proteasome

• head

• 20S core complex

• ATPase-ring

• base

• lid

1. Pan binding via ATP

2. Protein binding

3. ATPase activaton

4. Unfolding vis ATP

5. Translocation

CHIP-mediated protein degradation in the cytosol

• degredation of irreperable chaperone

• interarcts with TPR domain with HSP70 and HSP90

• U-box domain confers ubiqutinin ligase activity

• Ubiquitylates chaperone substrates in chaperone depndenr manner

• Chaperones try to save the protein.

• CHIP decides it is beyond repair.

• CHIP tags it with ubiquitin.

• The proteasome destroys it.

• binding HspB8 tagged for autophagy

• removal of aggregates

1. Isolated membrane

2. cargo of protein organeööed

3. Phagophore vesicle elongation

4. docking and fusion of autophagosome

5. lysosyme attachs

6. autolysosome

1. Chaperone-medaited auotophagy

2. Endosomal microautophagy

3. chaperone-assisted selective autophagy