9: protein folding

Question 1

ER: what?

Answer 1

multifunctional organelle responsible for biosynthesis, folding, assembly and modification of a large number of different soluble and membrane bound proteins, lipid metabolism. steroids metabolism, detoxification, calcium homeostasis, also communicates with nucleus, mitochondria, plasma membrane

Question 2

what do molecular chaperones do?

Answer 2

support protein folding: slow down process, bind to misfolded proteins, increase quality control

Question 3

what do folding sensors do

Answer 3

sense misfolded proteins and interact with peptide, send back into QC cycle

Question 4

folding factors: what do they do?

Answer 4

enzymes: accelerate protein folding (rate limiting steps). disulfide bond formation, isomerization

Question 5

2 examples of folding factors

Answer 5

PDI. ERp57

Question 6

folding sensor example (1)

Answer 6

UGGT

Question 7

3 molecular chaperones (3)

Answer 7

calnexin, calreticulin, BIP

Question 8

how do PDIs work? oxidized vs. reduced?

Answer 8

electron transport system. reduced PDI for isomerization. oxidized PDi for formation of disulfide bonds

Question 9

2 roles of molecular chaperones

Answer 9

reduce rate of protein folding + increase efficiency of folding in vivo

Question 10

BiP: does what?

Answer 10

interacts with completely unfolded peptide dependent on ATP hydrolysis, hydrophobic effect

Question 11

GRP94

Answer 11

interacts after BiP with partially folded peptide in ATP dependent manner, but with no hydrolysis of ATP (more of a holdase, allowing interaction with other chaperones)

Question 12

CRT/CNX action

Answer 12

interact after BiP with partially folded peptide containing N-linked monoglucosylated carbohydrate, non-ATP dependent

Question 13

PDI family: does what? speed? might need?

Answer 13

disulfide bond formation. slow. requires catalyst

Question 14

2 roles of chaperones in the ER?

Answer 14

facilitate the folding of proteins, slow down the folding process. increase the quantity and quality of correctly folded protein and maintain homeostasis

Question 15

quality control system: prevents? retains? favors?

Answer 15

prevents deployment of aberrant protein conformers. retains precursor proteins in an enviornment suitable for their maturation. favors correct assembly by increasing subunit concentration.

Question 16

summary: QC system reduces risks of? maintains?

Answer 16

reduces risks of proteotoxicity by inhibiting aggregation and degrading terminally mis-folded proteins. maintains homeostasis in early secretory pathway

Question 17

summary: QC system - regulation? stores? regulates?

Answer 17

developmental regulation of protein secretion. stores proteins for regulated secretion (plants, adipocytes). regulates ER stress responses

Question 18

what happens when ER homeostasis is disrupted by intrinsic/estrinsic factors?

Answer 18

calcium depletion, mutation in nascent protein, mutation in machinery, transport disruption, over-expression, energy deficiency, nutrient deficiency, oxidative stress, environmental factors, etc.

Question 19

how does ER respond to homeostasis disruption?

Answer 19

activation of corrective strategeies and coping responses. activation of UPR = translational attenuation, transcriptional activation of chaperone genes, protein degradation