BICD 110 Lecture Notes - Lecture 7: Hydrolase, Lysosome, Clathrin
28 Jun 2018
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BICD110 Lecture 7 Notes 4/24/18
- Major functions of the ER
o1) site of protein folding for proteins in the secretory pathway
newly translated protein is folded correctly in the ER
correct ER folding requires chaperones = BIP
folding also often requires correct glycosylation
problem: if protein not folded correctly, is trapped in the ER
ex: the mutant cystic fibrosis protein has channel missing 3
nucleotides, so trapped in the ER, and channel cannot exit ER
o2) site of disulfide bond formation
enzyme disulfide isomerase helps protein form correct disulfide bonds
allows proteins to search quickly though different S-S bonds to be
in the lowest free energy form of the protein, which helps the
protein assume its correctly folded state
play big role in proteins for secretory pathway
the cytoplasm has a different environment from ER and the
downstream organelles in the secretory pathway
cytoplasm: reducing environment; proteins use few disulfide bonds
ER lumen, downstream organelles, and outside cell have oxidizing environments,
so proteins more stable with disulfide bonds
o3) some proteins don’t fold correctly, so the ER is the site
of quality control
proteins that fail to fold correctly are retro-
translocated (out of ER) and destroyed by proteasome
retrotranslocation: if misfolded protein is found in ER,
goes through channel into cytosol. Ubiquitin (76 AA
peptide) recognizes and attaches to misfolded protein
for transport to proteasome for degradation into amino acids
o4) site of core glycosylation
a core oligosaccharide is put onto new ER protein by oligosaccharyl
transferase making a glycoprotein
changing only one or two carbohydrates on the oligosaccharide can
totally change the function of the glycoprotein
occurs during translation: on the growing peptide chain,
oligosaccharyl transferase = ER resident protein, adds
oligosaccharides. Has KDEL residue to keep it in the ER
proteins can undergo multiple core glycosylations
advantages of adding oligosaccharides
1) helps new protein assume its correctly folded conformation
oexperiment: if glycosylation blocked by adding the drug tunicamycin to cells,
many proteins are trapped in the ER and degraded by retrotranslocation
find more resources at oneclass.com
find more resources at oneclass.com
Document Summary
Major functions of the er: 1) site of protein folding for proteins in the secretory pathway. Newly translated protein is folded correctly in the er correct er folding requires chaperones = bip folding also often requires correct glycosylation. Play big role in proteins for secretory pathway the cytoplasm has a different environment from er and the downstream organelles in the secretory pathway cytoplasm: reducing environment; proteins use few disulfide bonds. Er lumen, downstream organelles, and outside cell have oxidizing environments, so proteins more stable with disulfide bonds: 3) some proteins don"t fold correctly, so the er is the site of quality control. Proteins that fail to fold correctly are retro- translocated (out of er) and destroyed by proteasome retrotranslocation: if misfolded protein is found in er, goes through channel into cytosol. Occurs during translation: on the growing peptide chain, oligosaccharyl transferase = er resident protein, adds oligosaccharides. Has kdel residue to keep it in the er.
