Lecture 12 ubiquitin Flashcards
(31 cards)
What is selectivity?
The ways of achieving the correct binding
What is avidity and affinity?
The ways of achieving tight binding
What is the half life of proteins definition?
The time it takes for the copy number to fall by half due to a specific protein system e.g., ubiquitination. Cyclins and transcription factors have half lives of seconds due to the quick signal pathway.
What percentage of proteins is turned over every day?
5%. Every single protein in the body is replaced every 6-12 months.
What is ubiquitin?
A covalent modifier that can signal selective degradation of other proteins via the UPS.
What is autophagy?
The other major intracellular pathway of protein degradation-ubiquitin plays a role here as well. Lysosome mediated degradation.
How does ubiquitin exert its effects?
By establishing new non-covalent protein protein interactions with the modified protein (alters interaction landscape).
How does neurons being post mitotic affect them?
They can’t divide to relieve themselves of pathological protein burden. Therefore they have incredibly active protein degradation systems. Ubiquitin aims to prevent those misfolding events from forming pathological proteins that lead to neurodegeneration.
What residue protrudes from the globular structure?
C-terminus (glycine 76) protrudes from the globular structure.
How many different PTMs have been found?
Between 300-400 PTMs that have been described. Reversible PTMs.
How does ubiquitin bind to proteins?
Side chains of selected lysine (K) residues (At NH2 group) in a modified protein become involved in a covalent isopeptide bond with the C terminal -COOH group of ubiquitin Gly76.
How do polyubiquitin chains form?
All of the 7 lys residues of ubiquitin (and Met at the N-terminus) can be used to form chains with different topologies and structures. This gives rise to the formation of Lys48-polyubiquitin chains.
What are the lysines?
Acceptor sites of ubq modification.
What is the proximal ubiquitin called?
The ubiquitin bound to the target protein.
What is the distal ubiquitin?
The last ubiquitin in the chain.
Why can N terminus methionine also be ubiquited?
It has a free amino group. This forms a peptide bond not an isopeptide bond.
How can western blots show how common ubq is as a PTM?
Many bands. Smear of activity with a free ubiquitin band at the bottom at 8.5kDa. The smear shows ubiquitinated proteins.
What is a covalent thiolester linkage?
S-Cys
What is the explanation of what the covalent thiolester linkage looks like?
A free sulf-hydryl group on a cysteine residue side chain and an S-H group interacting or forming a covalent bond with the free carboxyl group in glycine 76 at the C terminus of ubq.
What does ATP do in the ubq pathway?
Allows ubiquitin to bind to E1 and E2.
What are deubiquitinating enzymes?
Reverse ubiquitination (about 90 genes in humans). Associated with many human cancers.
What does monoubiquitylation lead to?
Endocytosis, protein sorting, subnuclear trafficking, gene expression.
What does polyubiquitylation lead to?
Degradation, DNA repair, signal transduction, proteolysis-independent unknown functions, proteosome binding.
How is ubiquitin recycled?
By proteosome associated DUBs
