Flashcards in Endocytosis and Protein Degradation Deck (14):
Routes for small volume endocytosis (2)
Phagocytosis: engulfing of material followed by delivery to lysosome.
Pinocytosis: small volume endocytosis mediated by ligand/receptor uptake via clathrin or caveolae.
Receptor binds cargo, R recognized by cytoplasmic adaptor, clathrin associates, dynamin pinches off vesicle.
Quality control in ER
30% of protein gets misfolded and degraded because they will otherwise aggregate
ER provides oxidation environment for folding and oligomeric assembly
Hsp 60 and Hsp 70
Hsp60: ATP-dependent, places protein in isolation chamber, "pulls" protein to have it "spring back" into correct conformation.
Hsp70 (BiP): Binds to hydrophobic regions of protein during folding
thiol oxidoreductase, assists with disulphide bond formation. Associates with Calnexin and Calreticulin
Calnexin and Calreticulin
Calnexin (trasmembrane) and Calreticulin: ER proteins that bind glucose residues added to proteins in ER and promote interactions with folding proteins. Glucose cleaved with dissociation.
Adds glucose to UGGT sequence of protein (marker for misfolding). Causes association with Calnexin/Calreticulin to promote folding assistance.
Requires 4+ ubiquitin chain on lysine residue
Addition of Ubiquitin process
1. E1 (activation) adds Ubq to E2 protein
2. E2 (conjugation) carries Ubq and associates with E3
3. E3 (ligation) recognizes protein and transfers Ubq from E2 to lysine residue or other Ubq
Protein at Proteasome
ATP utilized to unfold protein. Protein is fed into antechamber of proteasome composed of alpha subunits.
Protein enters central chamber of beta subunits which cleave protein into 7-9 AA pieces.
No ATP is required for cleavage.
caspase-like activity for acidic AAs
trypsin-like activity for basic AAs
chymotrypsin-like activity for hydrophobic AAs