Lecture 05 - Post Translational Modification Flashcards
What is the primary structure of a protein
the amino acids
Why does the order of the amino acids in primary structure matter
it increases the probability of certain amino acids interacting in further structures
What is the secondary structure of a protein
alpha helices, beta strands
What is the tertiary structure of a protein
folded helices and strands into domains
What is the quaternary structure of a protein
the functional assemblies of chains when 2 or more subunits come together
What are common post-translational modifications
phosphorylation, glycosylation, protein cleavage, ubiquitination
Where can phosphorylation occur
on serine, threonine or tyrosine residues
Is phosphorylation reversable
yes
What is phosphorylation used for
regulation in signal pathways in cells
What are the effects of phosphorylation
it adds a strong negative charge to the area which interacts with positive charges and repels negative charges
What is seen in alzheimers disease
amyloid beta plaques and Tau neurofibrillary tangles which an be detected in blood
What marker is being used to predict alzheimers
phosphorylation at residue 217 of tau
What is protein cleavage
proteases cut proteins to create or remove functions
Why do we not want proteases to work all the time
its an irreversible change and would just keep cutting proteins at random
How do we control where proteases cut
each protease has a unique sequence before/after the cut site to indicate where to cut
Where do we see proteases being used
in the blood clot pathway, each time a factor is made active it is cleaved by a protease
How do we prevent clotting from happing at random
the thrombin active site is shielded until it is cleaved at R320 and R271 which causes a conformational change in the protein revealing the active site
Where does glycosylation occur
in the ER
How does glycosylation work
complex mannose and glucose trees are added to specific asparagine molecules which effect the folding of the protein
only certain sequences get glycosylated (need signal sequences around it)
How does HIV use glycosylation to evade the immune system
it adds glycans to the outside of the protein which makes it hard for the host to make antibodies (antigens are not accessible), it also makes it hard for the immune system to recognize it as glycans are host structures
What is ubiquitination
tagging of a protein with ubiquitin which signals it for degradation
What is ubiquitin
a protein with lots of lysine residues
What are the steps of ubiquitination
- E1 attaches to Ubiquitins C-terminus
- asses Ubiquitin to E2 which recognizes different types of E3
- E3 specifies which substrate to get rid of
- more ubiquitin is added by the C-terminus to the Lys 48 of the previous ubiquitin
- the ubiquitin chain signals the complex to be brought to the proteasome
What does the proteasome do
it recognizes, unfolds and degrades ubiquinated proteins
What does the 19S of the proteosome do
accepts and unfolds proteins
What does the 20S of the proteosome do
contains proteases that chew up the proteins so the amino acids can be reused
How is the proteasome regulated
the proteases are facing into the barrel so only things that are accepted are degraded
Why does inhibiting proteases work as cancer drugs
- cancer cells need to make lots of proteins
- cancer cells need to degenerate lots of proteins to move through the cell cycle and divide
- the inhibition effects regular cells too but they are less dependant so the effects aren’t as great
