Lecture 40 - Protein Folding Disorders Flashcards Preview

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Flashcards in Lecture 40 - Protein Folding Disorders Deck (22):
1

In this folding disorder, a protein is mis-folded and may remain in its location of production, instead of being trafficked elsewhere.

What is this called?

Improper localization

2

Two "sub-disorders" may occur in improper localization. What are they?

Loss-of-function: An organ does not receive the proper proteins due to mis-folding. This prevents the organ from functioning properly.

Gain of f(x) toxicity: mis-folded proteins remain in location of synthesis. They may be active, and degrade the tissue in which they reside.

3

Occasionally, DNA undergoes a genetic change in which newly formed proteins interfere with the wild-type. This is known as _____.

dominant negative mutations

4

What is the amyloidogenic sequence in proteins?

VQIVY

5

When mutations to the CFTR membrane ion channel occur and the protein escapes degradation in the ER, the disease ______ occurs.

Cystic fibrosis

6

Mutations to the alpha-aminot trypsin protein result in the protein remaining localized in the liver. What occurs after?

Improper localization leading to degradation (trypsin=protease) of liver tissue; gain of f(x) mutation

7

A mutant protein produced by a mutation may cause weak filaments in the cytoskeleton of integumentary cells. What is this condition and what is mis-folding type?

Keratin epidermolysis bullosa;

dominant negative mutation

8

APOE4 is a protein change resulting in a ____ between amino acids. This is what type of mis-folding? What disease is it associated with?

salt-bridge; gain-of-toxic function; Alzheimer's (mt disfunction)

9

A common mechanism of cellular destruction in amyloid fibers is ____.

formation of a cell membrane pore from the beta-amyloid fibers.

10

Pores associated with beta-amyloid fibers produce what effect to the cell?

Lysis due to cell membrane damage

11

Outline the process of amyloid plaque formation.

a) seeding/nucleation

b) fibril formation

c) deposit of fibers (ex: Lewy bodies in Parkinson's Disease)

12

Aggregate formation can be blocked by stabilizing molecules and ______.

a. antibodies for specific sequences
b. changes to extracellular pH
c. disruption of amyloid plaques
d. genetic recombination with retroviruses

a. antibodies for specific sequences

13

What are the "keystones" for reaction to environmental stressors?

Detect
Respond
Adapt

14

By applying moderate levels of stress to an organism, it is believed that it could trigger adaptive stress defense pathways, allowing longer life. An example is "caloric restriction." What is this process called?

Hormetic stress

15

Proteostasis requires protein production, proper folding, and degradation of damaged/mis-folded proteins. What is the response to damaged/mis-folded proteins known as?

a. HSPS (Heat Shock Protein System)
b. UPD (Unfolded Protein Degradation)
c. UPR (Unfolded Protein Response)

c. UPR (Unfolded Protein Response)

16

In the Heat Shock Response, ____ manages degraded proteins.

A. HSF1
B. HSP90
C. HSF60

A. HSF1

17

What three things are required for the unfolded protein response in the ER?

- Inositol requiring element 1 (IRE1)

- PERK

- ATF6

18

What is the "last line of defense" regarding the management of mis-folded proteins?

Apoptosis. If the cell cannot manage the protein, it is better for the cell to die.

19

What are the two major chaperone systems of the mitochondria?

mtHSP70
HSP60-HSP10

20

This is specific to the mitochondria and is responsible for the degradation of mitochondrial proteins.

Protein Quality Control protease

21

What senses an "overload" in the PQC protease system?

UPRmt. It activates the transcription of nuclear encoded protective genes.

22

When cellular mechanisms are overwhelmed, mis-folded proteins may begin to accumulate. What type of protein folding disorder is this?

Improper degradation