Lecture 05 - Post Translational Modification

Question 1

What is the primary structure of a protein

Answer 1

the amino acids

Question 2

Why does the order of the amino acids in primary structure matter

Answer 2

it increases the probability of certain amino acids interacting in further structures

Question 3

What is the secondary structure of a protein

Answer 3

alpha helices, beta strands

Question 4

What is the tertiary structure of a protein

Answer 4

folded helices and strands into domains

Question 5

What is the quaternary structure of a protein

Answer 5

the functional assemblies of chains when 2 or more subunits come together

Question 6

What are common post-translational modifications

Answer 6

phosphorylation, glycosylation, protein cleavage, ubiquitination

Question 7

Where can phosphorylation occur

Answer 7

on serine, threonine or tyrosine residues

Question 8

Is phosphorylation reversable

Answer 8

yes

Question 9

What is phosphorylation used for

Answer 9

regulation in signal pathways in cells

Question 10

What are the effects of phosphorylation

Answer 10

it adds a strong negative charge to the area which interacts with positive charges and repels negative charges

Question 11

What is seen in alzheimers disease

Answer 11

amyloid beta plaques and Tau neurofibrillary tangles which an be detected in blood

Question 12

What marker is being used to predict alzheimers

Answer 12

phosphorylation at residue 217 of tau

Question 13

What is protein cleavage

Answer 13

proteases cut proteins to create or remove functions

Question 14

Why do we not want proteases to work all the time

Answer 14

its an irreversible change and would just keep cutting proteins at random

Question 15

How do we control where proteases cut

Answer 15

each protease has a unique sequence before/after the cut site to indicate where to cut

Question 16

Where do we see proteases being used

Answer 16

in the blood clot pathway, each time a factor is made active it is cleaved by a protease

Question 17

How do we prevent clotting from happing at random

Answer 17

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

Question 18

Where does glycosylation occur

Answer 18

in the ER

Question 19

How does glycosylation work

Answer 19

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)

Question 20

How does HIV use glycosylation to evade the immune system

Answer 20

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

Question 21

What is ubiquitination

Answer 21

tagging of a protein with ubiquitin which signals it for degradation

Question 22

What is ubiquitin

Answer 22

a protein with lots of lysine residues

Question 23

What are the steps of ubiquitination

Answer 23

1. E1 attaches to Ubiquitins C-terminus
2. asses Ubiquitin to E2 which recognizes different types of E3
3. E3 specifies which substrate to get rid of
4. more ubiquitin is added by the C-terminus to the Lys 48 of the previous ubiquitin
5. the ubiquitin chain signals the complex to be brought to the proteasome

Question 24

What does the proteasome do

Answer 24

it recognizes, unfolds and degrades ubiquinated proteins

Question 25

What does the 19S of the proteosome do

Answer 25

accepts and unfolds proteins

Question 26

What does the 20S of the proteosome do

Answer 26

contains proteases that chew up the proteins so the amino acids can be reused

Question 27

How is the proteasome regulated

Answer 27

the proteases are facing into the barrel so only things that are accepted are degraded

Question 28

Why does inhibiting proteases work as cancer drugs

Answer 28

1. cancer cells need to make lots of proteins
2. cancer cells need to degenerate lots of proteins to move through the cell cycle and divide
3. the inhibition effects regular cells too but they are less dependant so the effects aren’t as great