Protein Folding and Quality Control Take Place Within the ER

Question 1

what happens after polypeptides are released into the ER lumen?
what facilitates these foldings?

Answer 1

• after polypeptides are released into the ER lumen, they fold into their final shape
• molecular chaperones facilitate these foldings and assembly events

Question 2

most abundant molecular chaperone?

Answer 2

most abundant chaperone in the ER lumen is a member of the Hsp70 family of chaperones know as BiP (binding protein)

Question 3

• How does BiP work? what does it prevent?
• What else does BiP prevent?
• What does BiP then do?
• what happens if the polypeptide folds incorrectly?

Answer 3

• BiP acts by binding to hydophobic regions of polypeptide chains and prevents aggregation of polypeptides with similar regions
• BiP prevents interaction between hydrophobic regions of different proteins
• BiP than releases the polypeptide chain, accompanied by ATP hydrolysis, giving the polypeptide a brief opportunity to fold
• the hydrophobic region is buried in the interior of the molecule, and if it folds incorrectly it interacts with BiP again

Question 4

Protein folding is often accompanied by?

Answer 4

the formation of disulfide bonds

Question 5

Protein folding is often accompanied by formation of disulfide bonds: what is this reaction facilitated by? when does this act? what does it allow?

Answer 5

facilitated by protein disulfide isomerase, which acts before the synthesis of the polypeptide is complete allowing various types of disulfide bonds to be tested until the most stable arrangement is found

Question 6

Proteins that repeatedly fail to fold properly activate various quality control mechanisms: 2 mechanisms…

Answer 6

1. Unfolded protein response (UPR)

2. the ER associated degradation (ERAD)

Question 7

Proteins that repeatedly fail to fold properly activate various quality control mechanism: unfolded protein response

Answer 7

sensor molecules in the ER membrane detect misfolded proteins, which activate signaling pathways that shut down synthesis of most proteins while enhancing the production of proteins needed for folding and degradation

Question 8

Proteins that repeatedly fail to fold properly activate various quality control mechanisms: the ER associated degradation

Answer 8

recognizes misfolded or unassembled proteins and exports them back across the ER membrane to the cytosol, where they are degraded by proteosomes