1.5 Flashcards
Which enzyme helps untangle and refold aggregated proteins?
Chaperones
What is a common feature that enzymes interacting with mis-folded proteins shared with one another to enable physical interaction with their protein substrates?
Hydrophobic surface
HSP100
A chaperone protein that helps unfold proteins that are aggregated together
Which peptidyl prolyl isomerase requires post translational modification of the substrate protein for recognition and subsequent proline isomerization
PIN1
What does ATP hydrolysis to ADP cause to happen in HSP70
Closing of the lid in the substrate binding domain
What stabilizes amyloid fibril beta strands
-ionic interactions between charged side chains
-hydrophobic interactions between non polar side chains
Cyclophilins
-Peptidyl-prolyl isomerases
-can change proline cis to trans
FK506 Binding Proteins
-PPI
-Turns proline cis to trans
PIN1
-targets proteins that has a serine or threonine before proline
-alters proline cis to trans
-only recognizes after serine and threonine has been phosphorolyzed
HSP60 & HSP10
-chaperone
-primary folding chaperones
-GrOES and GroEL
HSP70
-delivery chaperone
-regulates translocation to ER
-delivers unfolded proteins to other chaperones
HSP100
-unfolding protein
-unfolds misfolded or aggregated proteins
What are the 3 componentes of the u folded protein response?
- Halting translation
- Increasing the # of chaperones to help with folding
- Target misfolded proteins for degradation
What happens if the unfolded protein response fails?
The cell will undergo programmed cell death/apoptosis
How is the accumulation of unfolded proteins recognized,
BIP
How does BIP work?
BIP is normally with the proteins ATF6, IRE1, and PERK. When unfolded proteins build up in the ER, it leaves its proteins which activates them
PERK1
-stops translation of new proteins when it phosphorylates the translation imitation complex
ATF6
-in the golgi ATF6 is cleaved to release and activate the transcription factor domain which turns on genes that help clean up
IRE1
-multifunctional protein
-splices mRNA
-degrades mRNA transcripts
-induces apoptosis
What is ubiquitin?
A small protein
What does Ubiquitylation of Lys residues do?
Targets protein for degradation by the 26S proteosome
How are amyloid beta strands highly stable?
- Salt bridge between lysine and aspartate
- Hydrophobic interactions between strands