Protein Folding Disorders

Question 1

What are the components of the cellular quality control system?

Answer 1

Proteasomes

Autophagy

ERAD (ER-associated degradation).

Question 2

What are some abnormalities in protein folding?

Answer 2

Improper degradation

Improper localization

Dominant negative mutations

Gain-of-toxic function

Amyloid accumulation

Question 3

You are studying protein folding and examine a group of cells that have overactive cellular degradation systems. What is the result of this?

Answer 3

mutant, misfolded, incomplete degraded proteins.

Question 4

Incorrectly folded proteins lead to improper subcellular localization

Answer 4

loss-of-function

gain of function toxicity

Question 5

What is a key modulator in protein homeostasis?

Answer 5

molecular chaperons

Question 6

How does a mutant protein affect the function of wild-type protein?

Answer 6

It causes a loss of protein activity and interferes with the function of the protein at cellular and structural levels.

Question 7

Protein conformational changes cause dominant phenotypes. What is the result of this?

Answer 7

Toxic proteins are made.

APOE4 disrupts mitochondrial function.

Superoxide dismutase is present

SRC kinases in cancer.

Question 8

What are amyloid fibers?

Answer 8

Insoluble protein aggregates.

Question 9

What is the sequence of amyloidogenic proteins?

Answer 9

VQIVY

It causes amyloid-related diseases

Question 10

What do lower order oligomers cause?

Answer 10

Toxic effects.

Amyloid deposits could be a protective mechanism

Question 11

What kind of structure do several amyloidogenic proteins form?

Answer 11

A pore like structure.

This disrupts the cell membrane integrity.

Question 12

In what individuals are misfolded forms of the protein frequently observed in?

Answer 12

The elderly

Those with mutations in the protein early in life.

Question 13

How do amyloids progess to amyloid plaques?

Answer 13

Seeding

Fibril formation

Deposit

Question 14

What is a potential remediation process of amyloid buildup?

Answer 14

Blocking aggregate formation.

THis can be done with antibodies that recognize conformational changes and specific sequences.

Question 15

How does hormetic stress affect an individual?

Answer 15

Applying moderate levels of stress could trigger beneficial and adaptive stress defense pathways, allowing longer life.

Question 16

What is proteostasis?

Answer 16

Maintenance of protein homoeostasis.

Question 17

What does proteostasis require?

Answer 17

Protein production

Folding

Degradation

Question 18

What are unfolded protein responses?

Answer 18

Complex pathways to ensure proteostasis in different compartments.

They are found in the cytosol, ER and mitochondria

Question 19

When is the apoptotic pathway used?

Answer 19

It is used last; it is the last line of defense.

Question 20

What is heat shock repsonse?

Answer 20

A response that manages denatured proteins in the cytosol.

Question 21

What are the two major mitochondrial chaperone systems?

Answer 21

mtHSP70

Multimeric protein HSP60 - HSP10

Question 22

How many proteins of the ETC are encoded by mtDNA?

Answer 22

13

Question 23

What are protein quality control proteases?

Answer 23

They recognize and degrade the proteins that do not fold.

They are also properly assembled.

Question 24

What is the functio of UPRmt?

Answer 24

It senses the overload of the QC system capacity.

It activates the transcription of nuclear encoded protective genes and re-establishes the mitochondrial homeostasis.

Question 25

What is a limitation of the UPRmt signaling?

Answer 25

The signal transmission from the unfolded/misfolded mitochondrial proteins to the nucleus cannot be accomplished using HSR and UPR system.

Question 26

What system assists in signal transmission from the unfolded/misfolded mitochondrial proteins to the nucleus?

Answer 26

retrograde response