Protein Folding and Misfolding Flashcards
In what compartments of the cell does protein folding occur?
*Cytoplasm *ER Mitochondria Chloroplasts Peroxisomes Others
Where does protein synthesis occur?
Ribosomes
What are types of covalent modifications of proteins?
Glycosylation
Phosphorylation
Acetylation
What end of the polypeptide chain is synthesized first?
N terminus
The native conformation of a protein is its ______ energy state
lowest
What do chaperones do?
Prevent inappropriate contacts during protein folding. e.g. protecting hydrophobic regions
How do chaperones speed up folding?
By restricting the folding pathway so the number of possible intermediate states is limited
Do chaperones change the thermodynamics of protein folding?
No!
What are three common protein families of chaperones?
*Hsp 70 *Hsp 60 (chaperonins) Hsp 90 * = most common
How were chaperones first discovered?
heat shock experiments
Do chaperones use ATP to fold the protein?
Yes
What causes the clamp of the hsp to close? What does this facilitate? What follows?
ATP hydrolysis brings the relevant pieces of the protein together
Then ADP is exchanged for ATP (?)
What is Hsp60 responsible for?
Folding OTC (responsible for breaking down urea) within the mitochondrial membrane
What are the two subunits of Hsp60? Which one is the cap?
GroES and GroEL GroES is the cap
Can folded proteins enter organelles?
No! Must enter in the unfolded state through protein-conducting pores
What is BiP?
An important Hsp70 chaperone in the ER
What does BiP do?
binds to hydrophobic regions of translocating proteins in the ER
Are unfolded proteins dangerous?
Yes when they accumulate they can stick together and cause problems
What is the UPR? Where does it occur?
Unfolded protein response that occurs in the lumen of the ER
What role does BiP play in the UPR?
BiP is upregulated/increased expression to take care of the accumulation of unfolded proteins in the ER
BiP attaches to the unfolded proteins which is sensed by the cell causing a protein kinase, PERK to increase gene expression of chaperone-coding genes
PERK also reduces the number of proteins entering the ER until the ER can catch up
Where are misfolded proteins degraded?
The proteasome
What cell marker/signal attaches to proteins to tell the proteasome to degrade it?
Ubiquitin (forms a polyubiquitin chain)
What are the 2 subunits of the proteasome? Which one is the “core” which is the cap?
Alpha and Beta
beta = core
alpha = cap
