Question

Precursor oligosaccharides are transferred to the asparagine (N) immediately after that amino acid has reached the ER lumen during protein translocation. They are used as tags to mark the state of protein folding. By checking these tags, the ER determines which proteins are folded properly and can leave the ER. When and how is the protein targeted for degradation? Briefly explain in your own words how the ER “knows” that protein should be degraded.

Answer 1

ER‐associated degradation (ERAD) pathway is responsible for the missfolted protien degradation in ER. ERAD is a control pathway that identifies and mark the misfolded ER proteins. first a misfolded protein is identified by ER chaperones, and target the misfolded protien retro‐translocation pathway. Than the misfolded preotien is retro‐translocated across the ER. The major component of this channel is the Sel1L-Hrd1 membrane complex which facilitate the movement of defective protien to cytosol by retrotranslocation. When the protien emerges into the cytosol, it is ubiquitinated by the catalytic domain of Hrd1 that faces the cytosol, resulting in polyubiquitinaton. In the final step, the protien is taken into the cytosol by p97, and given to the proteasome for degradation.