Intro To Metalloprotein Homeostasis And Sensing Flashcards
at what levels is homeostasis controlled
At gene txn level
At post txn (mrna deg or translation reg)
Post translational ie sequestered/endocytosis of transporters and degradation
What is zitR an example of in a bacteria
A tf sensing metal conc and affecting it at the txn level of the transporter
What does binding of zinc to zitR do
Changes it’s confirmation so dna bd can now bind dna and block importer of zinc expression
Do the family of tf in bacteria always down regulate gene exp of transporters
No, can also enhance them eg increasing efflux exporters
Bacteria have product sensing ability too (indirect metal sensing) , what does haem bind when fe is plenty in bacteria
Iron response regulator
Irr
What does this do when haem binds
Triggers irr degradation, which irr usually binds dna and represses txn of haem synthesis, efflux and fe storage when fe is low
Now that fe is high doesnrnrepress these
Which metals don’t need exporters
Those with low affinity eg manganese
Which need exporters because of toxicity
Zinc, nickel, copper
Why does copper have no imported
Bacteria have no cytoplasmic copper containing enzymes
Why do transcription factors affinity for high affinity metals like cu and zinc have to be increased
Because need to be able to cause export and repress import even at low metal ion levels within the cell
Which tf in yeast allows for import of fe when fe is low
Aft1/2
Aft senses fe-s clusters. How
Fe taken up by mitochondria and then fe - s clusters made and transported out to be incorporated into proteins
This is then sensed by aft1 which at high fe will exit the nucleus and can’t activate fe import
At low fe translocates to nucleus
Which kinase phosphorylates and causes aft1/2 exit of nucleus during oxidative/ph and osmotic stresses
Hog1
What is the yeast copper sensing tf
Mac1
Which domain on mac1 does cu bind and block its importer txn ctr1
Activation domain
When is the ctr1 importer upregulated
During superoxide dismutase need in oxidative stress
In low fe, how can yeast adapt to this
They will degrade the mrna of processes unnecessarily using fe like heme synthesis or storage
Means more fe for things like dna repair pathways
What does the human zinc sensor mtf-1 initiate txn of if zinc binds
Metallothioeneins (bind and reduce metal toxicity)
When is zinc displaced from mt and binds Mtf-1
Cadmium, h202 or copper presence
Give examples of things that can be degraded or sequestered ie post translational mods
Zip4 zinc uptake transporter
Ctr1 copper importer
Ferroportin
What was the first metal dependant trafficking found
Atp7q and b for cu trafficking
Why are metal chaperones safe was to localise metals
They are specific for 1 metal only
Which protein in bacteria is an example of compartmentalisation as folding of the protein with cu occurs in periplasm
CucA
Why does folding of mncA occur in cytoplasm with Mn before it gets transporter to periplasm
Because it traps zinc by folding so cu can’t exchange it
