Protein folding and misfolding (Ross) Flashcards
Describe how Hsp70’s function
- Proteins bind to the open substrate binding domain
- ATP is hydrolyzed and the clamp closes on the protein
- ADP is exchanged for ATP and the clamp opens again
- The cycle is repeated until folding is complete
Describe the structure of Hsp70’s
It has a large ATPase domain that is connected to a clamp that consists of a substrate binding domain and a lid
How do chaperones recognize their targets?
They bind hydrophobic amino acids
Describe the structure of Hsp60’s
The core consists of two heptameric folding chambers and two lids. Each folding chamber and lid is independently functioning
Describe how Hsp60’s function
Proteins bind the hydrophobic binding sites on the core and enter the chamber. ATP binds to the core and the lid attaches. ATP is hydrolyzed and protein folding commences
BiP is an example of an important ___
Hsp70
Briefly describe the unfolded protein response
Receptors on the ER membrane sense unbound BiP at physiological levels. When more BiP is occupied with protein folding the unbound receptors signal their downstream targets to increase chaperone and lipid production, and proteolysis of misfolded proteins
Describe the structure of the proteosome
Consists of two hexameric “unfoldase” caps and a 4 ring heptameric core
How does the proteasome recognize its targets?
Polyubiquitin tags
How is ubiquitin attached to target proteins?
ATP is hydrolyzed and ubiquitin is attached to E1 via a thioester bond. E1 binds to the E2/E3 complex and transfers its ubiquitin. The E2/E3 complex binds the target protein and transfers its ubiquitin
What type of bonds join ubiquitin together?
Isopeptide bonds between the epsilon amine of lysine 48 on Ub 1 and the c-terminal glycine of Ub2
This ER enzyme promotes the formation of disulfide bonds
Protein disulfide isomerase PDI
How do calnexin and calreticulin work?
They bind glycoproteins that have been processed to have only 1 glucose residue. When the final glucose is removed, calnexin and calreticulin dissociate, allowing the properly folded protein to pass into the golgi
In order to be eliminated, proteins must be___ into ___ in an ATP dependent process
retrotranslocated into the cytoplasm
What’s the difference between JUNQ and IPOD as sites for misfolded proteins?
JUNQ recognizes poly-Ub proteins and degrades them
IPOD non-Ub proteins and stores them
