Lecture 12 - Protein homeostasis 2

Question 1

in which 2 locations in the cell are proteasomes located?

Answer 1

cytoplasm and nucleus

Question 2

proteolysis breaks which kinds of bonds? how many amino acids long are the products of proteolysis?

Answer 2

peptide, 7-8 amino acids

Question 3

name the 2 subunits and their functions in the 20S proteasome

Answer 3

alpha - maintains a gate through which substrates enter
beta - contain protease active sits on interior

Question 4

the 26S proteasome contains how many 19S and how many 20S proteasomes?

Answer 4

2 x 19 and 1 x 20

Question 5

in the 26S proteasome, what does the 19S cap contain (2 things)?

Answer 5

ATPase active sites and ubiquitin binding sites

Question 6

which 2 termini can be found on ubiquitin? which 2 lysine residues?

Answer 6

C and N termini, Lys 48, 63

Question 7

the E1 ubiquitin enzyme has how many types in mammalian cells? what does it activate?

Answer 7

only one type, activates ubiquitin

Question 8

the E2 ubiquitin enzyme has how many types in mammalian cells? what does it bind to?

Answer 8

several types, binds to activated ubiquitin

Question 9

the E3 ubiquitin enzyme has how many types in mammalian cells, giving an example? what does it interact with?

Answer 9

many different enzymes e.g Mdm2

interacts with E2 enzymes

Question 10

name the enzymes which reverse the action of ubiquitination, recycling ubiquitin

Answer 10

de-ubiquitinating enzymes (DUBs)

Question 11

name the 2 types of DUBs

Answer 11

USPs and UCHs

Question 12

Aggregated proteins called what? containing ubiquitin increase in which body part with age?

Answer 12

alpha-synuclein in retina

Question 13

name the 3 types of autophagy

Answer 13

macroautophagy, microautophagy, chaperone mediated

Question 14

which type of autophagy involves the elongation of the membrane and the sequestering of the cytoplasm in vesicles called autophagosomes which are then transported to lysosomes?

Answer 14

macroautophagy

Question 15

which type of autophagy is the least well understood with the lysosomal membrane internalising?

Answer 15

microautophagy

Question 16

in which type of autophagy does Hsp70 help transport to the lysosomal surface, binding to LAMP-2A where it then unfolds and disassembles?

Answer 16

chaperone mediated autophagy

Question 17

in parkinson’s name 2 mutant proteins which bind to LAMP-2A receptors and block them

Answer 17

alpha-synuclein, UCHL1

Question 18

in alzheimer’s name the mutant protein which binds to LAMP-2A receptors blocking them?

Answer 18

tau

Question 19

a protein aggregate is defined as a protein with a change in ….. or …. structure, has …. solubility in aqueous solvents and has an …… sub-cellular or extracellular localisation

Answer 19

secondary or tertiary
poor
aberrant

Question 20

in aggregated proteins what happens to the hydrophobic regions?

Answer 20

they are internalised

Question 21

The propensity of a protein to aggregate depends on which 3 things?

Answer 21

secondary structure, stability of tertiary structure and degree of disorder

Question 22

small protein aggregates come together to form a what? is this reversible once formed?

Answer 22

inclusion body, no it is irreversible

Question 23

an aggresome is a formation of many what? which cellular component of the cytoskeleton does an aggresome use to form itself?

Answer 23

inclusion bodies, microtubules