ER - PRO & Lipids (13) Flashcards
how does the cell deal with misfolded PROs?
A chaperone associates with a growing polypeptide as it emerges from the cytoplasm or ER, chaperones facilitate the proper folding by supressing or unfolding incorrect structures
Chaperones aren’t always necessary; AA sequence is prone to folding a desired way A misfolded PRO that cannot be corrected is exported & destroyed by the proteasome
how do chaperones facilitate proper folding?
suppressing or unfolding incorrect structures
what triggers the unfolded PRO response?
too many unfolded PROs are produced at once
ER has sensors that monitor the levels of unfolded PROS
The unfolded PRO response mechanism
When too many unfolded PROs accumulate, BiP releases from sensors to refold PROs & activating sensors. Sensors are released alerting the cell in various ways:
o Transcription factor sensor goes to nucleus & increases the production of chaperones
o Phosphorylated translation factor inhibit the small subunit enabling the folding process to catch up
o Can also, inactivate an initiation factor to prevent more translation
how do chaperones recognize misfolded PROs?
o Recognizes unfolded PROs by looking for hydrophobic regions on the surface
what induces the cell to make chaperones?
Heat shock
Cold shock
Anoxia
what can cause PRO-PRO aggregation?
hydrophobic regions on the surface on the PRO
How can bacteria survive heat shock?
bacteria are heated allowing the cell to accumulate enough HSPs, when the temperature increases the bacteria have enough of a dose that they are protected
what protects against cardiac failure? & where was this seen?
elevated Hsp70 (chaperone)
transgenic mice
kuru
neurological disorder first seen in Fore people of New Guinea
o Practiced cannibalism, once they stopped the disease stopped
o Uncontrolled motor control
caused by prions
scrapie
a disease in sheep & goats, staggering gait & strange behavior such as scraping off the coat due to neurological damage
caused by prions
mad cow disease
neurological damage causes loss of motor control, bovine spongiform encephalopathy (BSE)
caused by prions
variant creutzfeld-jacob disease (vCJD)
brain develops holes, results in loss of neurological function
o Due to consumption of contaminated mad cow beef
caused by prions
prion
abnormal PRO, change the shape of PROs into the wrong configuration (anti-chaperone PROs)
what is the mechanism behind the disease of kuru, scrapie, mad cow & vCJD?
presence of abnormal PROs known as prions
PrPC
normal prion, enriched in neurons, mostly alpha helices
PrPSC
mutant/disease form of the normal prion, same AA as the normal prion but is mostly beta sheets
what is the diff b/w the mutant & normal prion PRO?
same AA sequence
normal –> alpha helices
mutant/disease –> beta sheets
how do the normal prion cells become harmful? & why isn’t there a defense? & what is the outcome?
PrPSc acts as an anti-chaperone and transforms PrPC into PrPSc
Mutant PRO is too similar to its own
PrPSc will aggregate into fibers, no longer functional & will obstruct the CNS
why don’t PrpSc PROs become removed?
their shape somehow protects them from being processed by the cell’s machinery that is responsible for the removal of misfolded PROs
how does a proteasome recognize a misfolded PRO targetted for destruction?
Proteasome recognizes misfolded PROs that cannot be resorted. BiP (chaperone) transports the misfolded PRO into the cytoplasm through reverse translocation through a translocon. The PRO is tagged with ubiquitin
describe the structure of a proteasome
Globular PRO structure
not membrane-bound
4 rings, 7 subunits
where are proteasomes located?
nucleoplasm or cytoplasm
Do prokaryotes or eukaryotes have proteasomes?
both
