Key Terms with Example Questions Flashcards
ubiquitin
a 76 amino acid polypeptide that acts as a tag to identify misfolded, obsolete, and damaged proteins to be degraded by proteases or repaired by polyubiquitylation,
depending on whether it binds to lys 48 for degradation or lys 63 for repair
proteasome
has 3 parts (2 19s cap and 20s core)
chaperonin
Hsp60; a class of chaperones that act post-translationally and facilitate folding by their small chamber
degron
a sequence that marks a target protein as needing to be degraded; a signal to E3
hsp 70
aka HSC (heat shock cognate); acts co-translationally and functions to bind and stabilize unfolded/partly folded proteins to prevent aggregation while the new protein is still being translated because it does not know how to fold until fully synthesized;
- E3
ubiquitin ligase; attaches to the degron of a target protein to transfer ubiquitin from E2 to the lysine48 NH3 group, resulting with the polyubiquitin chain on the target protein
20s core
protease; has the active sites to clip every peptide bond and keeps the entire substrate bound until it is converted into amino acids
ubiquitin conjugating enzyme
E1; has a cysteine side chain (-SH) that attaches to ubiquitin (COO-) to form a thioester bond (S-C=O)
target protein
a protein that is marked or needs to be marked for either degradation, repair, etc.
For further thought: There are about 600 E3 ligases and 30 distinct E2 molecules. Why do you think there is such a big difference in the number of E3 and E2 molecules?
Application: Components of the ubiquitin machinery were identified independently in genetic screens for genes that regulate the cell cycle. A mutation in genes required for chromosome segregation should cause cells to arrest in mitosis before chromosome segregation occurs. As it turns out, in some of these mutants that arrested in mitosis before chromosome segregation, the gene product was required for proteolytic destruction of specific proteins. What do you think these specific proteins do? What does the unmutated form of the gene encode?
In your own words describe the overarching cell biology concept illustrated by these pathways?
Ubiquitin can also regulate histones by
monoubiquitylation and endocytosis by multiubiquitylation; attaches as a tag by an isopeptide bond
Ubiquitin receptor on 19s cap…
recognizes ubiquitin
Ubiquitin hydrolase on 19s cap…
clips ubiquitin