Lecture 4 "Protein folding and the quality control in the ER"

• Two Routes:

1. Glycosylated route

2. Non-glycosylated route

1. Protein is made on a ribosome and enters the ER through the translocon.

2. If it is glycosylated, OST, glucosidases, calreticulin, UGGT, and PDI handle folding control.

3. If it is not glycosylated, BiP, ERdj3, SDF2, and PDI guide folding in the ER lumen.

4. Properly folded proteins move on to secretion

1. Import

2. Chaperone binding

3. N-Gylcosilation

4. Folding

5. Export

• Calnrxin (CNX) and CRT (Calretitulin) can only bind to a single glucose

• has to cleave G14/G13

1. Direct recognition of irreparable damaged proteins trough specific features of the substrate

2. “Timer” (indirect mechansim)

1. Recognition

2. Ubiquitination

3. Retro-translocation

4. Degradation

• competitive action of UGGT and Manosidase

• Yos9 is an ER quality-control lectin and integral subunit of HRD ligase