HUANG - LECTURE 2

Question 1

what is phosphorylation

Answer 1

Question 2

what is lipidation

Answer 2

anchors to the membrane
reversible process: turn on and off by regulating the localization

Question 3

what is disulfide bond modification

Answer 3

covalently links the “S” atoms of two different cysteine residues
usually happens outside the cell, needs to be in a more oxidized environment
not a very common modification

Question 4

what is acetylation

Answer 4

Question 5

what can protein modifications do

Answer 5

Question 6

example of phosphorylation influencing localization

Answer 6

Question 7

example of phosphorylation influencing protein-protein interactions

Answer 7

Question 8

what can be glycosylated?

Answer 8

proteins and lipids

Question 9

different between a glycoprotein and a proteoglycan

Answer 9

Question 10

what are the functions of glycosylation

Answer 10

phosphorylation is prevented by O-linked glycosylation

Question 11

how is c-Myc regulated by both phosphorylation and glycosylation?

Answer 11

• c-Myc can be phosphorylated by ERK, which leds to its stabilization (on Ser62)
• it can also be phosphorylated (Thr58) again by GSK3beta, which promotes the removal of the Ser62 phosphate, and leads to the ubiquitination and degradation of c-Myc
• c-Myc can also be glycosylated by OGT on Thr58, which leads to its stabilization

Question 12

what are the modifications that can be done to sugars

Answer 12

Question 13

what are the primary sugars

Answer 13

Question 14

what are the different sugars and where are they made

Answer 14

Question 15

what are the most common sites of glycosylation

Answer 15

Question 16

what are the functions of O-linked glycosylation and where do those functions manifest?

Answer 16

protection and water retention are the major functions
shown in the ECM, synovial fluid in joints, mucus and others
also blocks phosphorylation

Question 17

when can glycosylation occur?

Answer 17

post or co translationally

Question 18

which enzymes are responsible for glycosylation and what motif do they recognise?

Answer 18

Question 19

what is the first step of biosynthesis of all N-linked oligosaccharides

Answer 19

Question 20

what is the structure of the precursor Glc3Man9(GlcNac)2

Answer 20

Question 21

what are the types of N-linked glycoproteins

Answer 21

high mannose, hybrid and complex

Question 22

what is the structure of dolichol

Answer 22

Question 23

what are the steps of Dolichol-PP-oligosaccharide synthesis

Answer 23

Question 24

what can now N-linked glycoproteins do?

Answer 24

Question 25

what happens for N-linked glycoproteins to mature in the ER?

Answer 25

Question 26

what happens to glycoproteins once they reach the golgi after being done in the ER?

Answer 26

nucleotide sugars don't have to be imported into the ER, as they are donated to dolichol and then flipped

Question 27

what are the relative amounts of High mannose, hybrid and complex sugars throughout the ER and the GA?

Answer 27

Question 28

how do the nucleotide sugars get into the golgi?

Answer 28

Question 29

example of the role of glycosylation in cancer

Answer 29

cancers upregulate PDL-1 (which is glycosylated) and bind to the PD-1 receptors on effector T cells this has an effect of immunosuppression and T cells cannot kill those cancer cells anymore a therapy sequesters those PDL1 receptors, and can also be endocytosed inside the cancer cell to induce cell death

Question 30

how can cancer altered glycosylation enter the bloodstream

Answer 30

Question 31

how are glycoproteins targeted to the lysosome?

Answer 31

Question 32

how are proteins brought from the GA to the lysosome?

Answer 32

Question 33

what does UGGT do?

Answer 33

reverse effect of glucosidase II adds sugar residues back involved in ER quality control processing

Question 34

how does the protein folding quality control work

Answer 34

Question 35

what happens if proteins still cannot properly fold despite multiple rounds with UGGT?

Answer 35

goes into ERAD (ER associated degradation) EDEM recognises misfolded proteins and recruits additional chaperones BiP escorts to the membrane, where it will be exported and degraded in the proteasome

Question 36

what is the UPR

Answer 36

if a lot of ERAD is happening, general protein synthesis is paused selective transcription/translation of chaperones, foldases, ERAD components and apoptosis