Protein Homeostasis and Aging

Question 1

Entire set of proteins expressed by a genome, cell, tissue, or organism under defined conditions

Answer 1

proteome

Question 2

a state of dynamic equilibrium where protein synthesis and folding are balanced with protein degradation

Answer 2

protestasis

Question 3

experimented with urea and found that all information required for protein folding is
provided by the amino acid sequence

Answer 3

Anfinsen’s experiment

Question 4

levinthal paradox

Answer 4

demonstrates that a purely random search for the correct conformation can’t work

Question 5

folding intermediates

Answer 5

accelerate folding

Question 6

a chaperone

Answer 6

a protein that interacts with, and aids in,
the folding or assembly of another protein without being part of its final structure

Question 7

most chaperones are

Answer 7

hsps, their synthesis is induced by stress

Question 8

how do chaperones work

Answer 8

Many chaperones act by binding exposed hydrophobic regions to prevent nonnative
interactions and protein misfolding

Question 9

atp dependent
Ubiquitous class of chaperones; constitutively
expressed and stress-induced members

Answer 9

Hsp70s

Question 10

hsp70 open state

Answer 10

atp bound

Question 11

hsp70 closed state

Answer 11

adp bound

Question 12

hsp40 co-chaperones with __ to do ___

Answer 12

with hsp70 to deliver misfolded substrates

Question 13

hsp90s

Answer 13

Regulation of protein complex assembly and
translocation

Question 14

which hsp is highly expressed in all species

Answer 14

hsp90s

Question 15

which hsp stabilizes a number of proteins required for tumor growth, investigated as anti-cancer drugs

Answer 15

hsp90s

Question 16

whose activity is coordinated by stress inducible phosphoprotein 1 (STl1)

Answer 16

hsp70 and hsp90

Question 17

which hsp is involved in disaggregation

Answer 17

hsp100s

Question 18

disaggregase yeast

Answer 18

hsp104

Question 19

mammalian disaggregase

Answer 19

HSP110 +HSP40 +HSP70

Question 20

which hsps are involved in prevention of aggregation

Answer 20

hsp 60s and shsps

Question 21

how do smallHSPs work

Answer 21

surround other proteins to control and sequester aggregates
act early

Question 22

chaperone functions

Answer 22

Folding/refolding of de novo and
misfolded proteins
Regulate protein complex formation
Mediate the response to proteotoxic
stress (heat shock, oxidative stress,
heavy metals, etc.)

Question 23

heat shock response

Answer 23

Cellular response to proteotoxic stressors
aimed at restoring protein homeostasis.

results in increased expression of chaperones

Question 24

HSF-1 is a…

Answer 24

transcription factor

Question 25

hsf-1 process

Answer 25

triggered by an increase in unfolded proteins chaperones are titrated away proteins Hsf1 homo-trimerizes and translocates to the nucleus to promote transcriptional activity of HSR gene

Question 26

secreted or proteins with hydrophobic domains can be properly folded and targeted here without aggregating.

Answer 26

ER

Question 27

ultimate goal of the UPRER response

Answer 27

decrease the concentration of misfolded proteins in the ER.

Question 28

what is UPRer response

Answer 28

a signaling pathway which relieves stress by selective gene upregulation and other mechanisms triggered by increase of unfolded proteins

Question 29

programmed ER stress leads to

Answer 29

apoptosis

Question 30

oligomerizes, autophosphorylates and activates its RNase domain to remove an intron from XPB-1 mRNA to facilitate its translation. XPB-1 then binds to specific promoters to activate transcription of UPR genes

Answer 30

IRE1

Question 31

phosphorylates eIF2α to block the formation of ribosomal pre-initiation complex and to attenuate translation, while at the same time preferentially translate the ATF4 transcription factor

Answer 31

PERK

Question 32

migrates to the Golgi upon UPR induction, where it is cleaved; it moves out to the nucleus and activates transcription from ER-stress responsive promoters.

Answer 32

ATF6

Question 33

mitochondria has its own

Answer 33

UPR

Question 34

Within a single cell, the mitochondria can signal to change

Answer 34

nuclear transcription

Question 35

RNAi disruption of a mitochondrial ETC gene, cco-1 can induce

Answer 35

UPR mito

Question 36

In C. elegans it is possible to knock down

Answer 36

genes in specific tissues Strategy: express a hairpin (HP) ds RNA; inverted repeat of a sequence can self anneal into a double stranded RNA

Question 37

Cell non-autonomous =

Answer 37

inactivate gene in one cell but see the effect in another

Question 38

Proteo-stress in the mitochondria of one cell (neuron) can be communicated to

Answer 38

induce protein-folding defense in another cell (intestine)

Question 39

Ubiquitin proteasome system (UPS)

Answer 39

Degrades unnecessary or damaged proteins through proteolytic activity of proteasomes

Question 40

Autophagy

Answer 40

Degrades unnecessary or dysfunctional cellular components through the actions of lysosomes (organelles, proteins, etc.)

Question 41

Ubiquitin itself contains 7 lysine residues to which another ubiquitin can be ligated, forming ---

Answer 41

polyubiquitin chains

Question 42

recognizes Lys-linked chains of 4 or more ubiquitins

Answer 42

proteasome

Question 43

Ubiquitin activating enzyme

Answer 43

E1

Question 44

Ubiquitin conjugating enzymes

Answer 44

E2

Question 45

Ubiquitin ligases

Answer 45

E3

Question 46

Ubiquitin process

Answer 46

Ubiquitin gets ligated to a substrate for degradation (more than once) Polyubiquitin directs to the proteasome, which deubiquitinates it, unfolds it, and degrades it

Question 47

hollow and provides a cavity with proteolytic activity

Answer 47

Proteasome 20S core particle

Question 48

recognize ubiquitinated proteins and regulate transfer to the catalytic core.

Answer 48

Proteasome 19S regulatory caps

Question 49

20s core α subunits

Answer 49

interact with the 19S caps and form a gate that blocks unregulated access to the core

Question 50

20s core b subunits

Answer 50

have the protease activity

Question 51

19S regulatory particle

Answer 51

binds atp ATP hydrolysis provides energy for substrate unfolding (required for transfer into narrow core) Removes ubiquitin chain from substrate Opens gate provided by α subunit in core

Question 52

Ubiquitin proteasome system

Answer 52

Degrades unnecessary or damaged proteins through proteolytic activity of proteasomes

Question 53

Autophagy

Answer 53

Degrades unnecessary or dysfunctional cellular components through the actions of lysosomes

Question 54

Lysosomes are

Answer 54

acidic

Question 55

Macroautophagy

Answer 55

Removes damaged organelles, aggregated proteins, lipids, and more * Double membrane structure fuses

Question 56

Microautophagy

Answer 56

* Direct engulfment of cytoplasmic material by lysosomes (organelles, proteins) * Lysosomal membrane invaginates and engulfs the cytoplasmic material directly

Question 57

Chaperone-mediated autophagy (CMA)

Answer 57

Lysosomal degradation of individual proteins * Selective autophagy pathway – Hsc70 recognizes KFERQ-like motif

Question 58

Chaperone and Hsf1 over-expression

Answer 58

improves lifespan