L8: Agbas Special Topic

Question 1

protein-folding relevant problems

Answer 1

improper degradation
improper localization
dominant-neg mutations
gain of toxic function
amyloid accumulation

Question 2

improper degradation

Answer 2

overactive cellular degradation systems can contribute to accumulation of mutant, misfolded, incomplete degraded proteins

Question 3

improper degradation of proteins can contribute to the development of ?

Answer 3

severe diseases

Question 4

improper localization

Answer 4

when proteins are misfolded they do not go to the correct places

resulting in:
loss of function
gain of toxic function

Question 5

dominant negative mutations

Answer 5

a mutant protein is antagonistic to the normal protein

interferes w/ normal function at cellular and structural levels

Question 6

gain of toxic function

Answer 6

protein conformational changes can cause dominant phenotypes

proteins become toxic

Question 7

APOE4

Answer 7

disrupts mito function

impairs neurite outgrowth

Question 8

APOE4

Answer 8

disrupts mito function

impairs neurite outgrowth

Question 9

define amyloid fibers

Answer 9

insoluble protein aggregates

Question 10

amyloidogenic proteins

Answer 10

have VQIVY sequences

can cause amyloid-related diseases

Question 11

some amyloidogenic proteins can form _____-like structure to disrupt ?

Answer 11

pore like

disrupt cell memb integrity

Question 12

misfolded forms of amyloidogenic proteins are frequently observed in ?

Answer 12

elderly as part of aging

early in life when individual has mutations

Question 13

rate the energy states of partially folded, native state and amyloid fibers/aggregates.

Answer 13

highest nrg = partially folded
native state
amorphous aggregates
amyloid fibers = lowest nrg state

Question 14

steps in progress from amyloid fibers to plaque formation

Answer 14

seeding = nucleation
fibril formation
deposit

Question 15

______ modifications enhances the formation of amyloid fibers.

Answer 15

covalent modifications

Question 16

______ modifications enhances the formation of amyloid fibers.

Answer 16

covalent modifications

Question 17

possible ways to block aggregate formation

Answer 17

use small molecules — as a stabilizer

site specific abs

Question 18

site-specific antibodies recognize ?

Answer 18

conformational changes

can be sequence specific

Question 19

keystones for environmental stressors – DRA

Answer 19

to detect
to respond
to adopt

Question 20

intrinsic induction of stress defense programs and resulting ________ can _______ _______ _______ .

Answer 20

adaptation

increase life expectancy

Question 21

hermetic stress

Answer 21

applying moderate levels of stress can trigger beneficial and adaptive stress defense pathways

allowing longer life
ex. vaccines

Question 22

caloric restriction prolongs

Answer 22

lifespan

Question 23

define proteostasis

Answer 23

protein homeostasis

Question 24

UPR

Answer 24

unfolded protein response

Question 25

proteostasis – cellular proteins

Answer 25

folded by chaperons

Question 26

membrane and secreted proteins are folded ?

Answer 26

fold and mature in ER

Question 27

the apoptotic pathway is the ________ defense for proteostasis.

Answer 27

last line of defense

Question 28

UPR - er

Answer 28

upr response when bad proteins accumulate in ER causing ER stress

this pathway is intended to save the cell

Question 29

UPR - mt

Answer 29

upr response when mito is under stress

UPR senses overload of the QC system capacity

Question 30

PQC

Answer 30

protein quality control - proteases

specific to mito compartments
–recognize and degrade bad proteins

Question 31

UPR-mt senses overload of _____ system capacity and activates ?

Answer 31

QC system

activates transcription of nuclear encoded protective genes

to re-establish the mito homeostasis

Question 32

chatty mitochondria

Answer 32

discovered that mitochondria can communicate w/ each other and w/ the nucleus