L8: Agbas Special Topic Flashcards
protein-folding relevant problems
improper degradation improper localization dominant-neg mutations gain of toxic function amyloid accumulation
improper degradation
overactive cellular degradation systems can contribute to accumulation of mutant, misfolded, incomplete degraded proteins
improper degradation of proteins can contribute to the development of ?
severe diseases
improper localization
when proteins are misfolded they do not go to the correct places
resulting in:
loss of function
gain of toxic function
dominant negative mutations
a mutant protein is antagonistic to the normal protein
interferes w/ normal function at cellular and structural levels
gain of toxic function
protein conformational changes can cause dominant phenotypes
proteins become toxic
APOE4
disrupts mito function
impairs neurite outgrowth
APOE4
disrupts mito function
impairs neurite outgrowth
define amyloid fibers
insoluble protein aggregates
amyloidogenic proteins
have VQIVY sequences
can cause amyloid-related diseases
some amyloidogenic proteins can form _____-like structure to disrupt ?
pore like
disrupt cell memb integrity
misfolded forms of amyloidogenic proteins are frequently observed in ?
elderly as part of aging
early in life when individual has mutations
rate the energy states of partially folded, native state and amyloid fibers/aggregates.
highest nrg = partially folded
native state
amorphous aggregates
amyloid fibers = lowest nrg state
steps in progress from amyloid fibers to plaque formation
seeding = nucleation
fibril formation
deposit
______ modifications enhances the formation of amyloid fibers.
covalent modifications
______ modifications enhances the formation of amyloid fibers.
covalent modifications
possible ways to block aggregate formation
use small molecules — as a stabilizer
site specific abs
site-specific antibodies recognize ?
conformational changes
can be sequence specific
keystones for environmental stressors – DRA
to detect
to respond
to adopt
intrinsic induction of stress defense programs and resulting ________ can _______ _______ _______ .
adaptation
increase life expectancy
hermetic stress
applying moderate levels of stress can trigger beneficial and adaptive stress defense pathways
allowing longer life
ex. vaccines
caloric restriction prolongs
lifespan
define proteostasis
protein homeostasis
UPR
unfolded protein response
proteostasis – cellular proteins
folded by chaperons
membrane and secreted proteins are folded ?
fold and mature in ER
the apoptotic pathway is the ________ defense for proteostasis.
last line of defense
UPR - er
upr response when bad proteins accumulate in ER causing ER stress
this pathway is intended to save the cell
UPR - mt
upr response when mito is under stress
UPR senses overload of the QC system capacity
PQC
protein quality control - proteases
specific to mito compartments
–recognize and degrade bad proteins
UPR-mt senses overload of _____ system capacity and activates ?
QC system
activates transcription of nuclear encoded protective genes
to re-establish the mito homeostasis
chatty mitochondria
discovered that mitochondria can communicate w/ each other and w/ the nucleus
