Intro To Metalloprotein Homeostasis And Sensing

Question 1

at what levels is homeostasis controlled

Answer 1

At gene txn level

At post txn (mrna deg or translation reg)

Post translational ie sequestered/endocytosis of transporters and degradation

Question 2

What is zitR an example of in a bacteria

Answer 2

A tf sensing metal conc and affecting it at the txn level of the transporter

Question 3

What does binding of zinc to zitR do

Answer 3

Changes it’s confirmation so dna bd can now bind dna and block importer of zinc expression

Question 4

Do the family of tf in bacteria always down regulate gene exp of transporters

Answer 4

No, can also enhance them eg increasing efflux exporters

Question 5

Bacteria have product sensing ability too (indirect metal sensing) , what does haem bind when fe is plenty in bacteria

Answer 5

Iron response regulator

Irr

Question 6

What does this do when haem binds

Answer 6

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

Question 7

Which metals don’t need exporters

Answer 7

Those with low affinity eg manganese

Question 8

Which need exporters because of toxicity

Answer 8

Zinc, nickel, copper

Question 9

Why does copper have no imported

Answer 9

Bacteria have no cytoplasmic copper containing enzymes

Question 10

Why do transcription factors affinity for high affinity metals like cu and zinc have to be increased

Answer 10

Because need to be able to cause export and repress import even at low metal ion levels within the cell

Question 11

Which tf in yeast allows for import of fe when fe is low

Answer 11

Aft1/2

Question 12

Aft senses fe-s clusters. How

Answer 12

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

Question 13

Which kinase phosphorylates and causes aft1/2 exit of nucleus during oxidative/ph and osmotic stresses

Answer 13

Hog1

Question 14

What is the yeast copper sensing tf

Answer 14

Mac1

Question 15

Which domain on mac1 does cu bind and block its importer txn ctr1

Answer 15

Activation domain

Question 16

When is the ctr1 importer upregulated

Answer 16

During superoxide dismutase need in oxidative stress

Question 17

In low fe, how can yeast adapt to this

Answer 17

They will degrade the mrna of processes unnecessarily using fe like heme synthesis or storage

Means more fe for things like dna repair pathways

Question 18

What does the human zinc sensor mtf-1 initiate txn of if zinc binds

Answer 18

Metallothioeneins (bind and reduce metal toxicity)

Question 19

When is zinc displaced from mt and binds Mtf-1

Answer 19

Cadmium, h202 or copper presence

Question 20

Give examples of things that can be degraded or sequestered ie post translational mods

Answer 20

Zip4 zinc uptake transporter

Ctr1 copper importer

Ferroportin

Question 21

What was the first metal dependant trafficking found

Answer 21

Atp7q and b for cu trafficking

Question 22

Why are metal chaperones safe was to localise metals

Answer 22

They are specific for 1 metal only

Question 23

Which protein in bacteria is an example of compartmentalisation as folding of the protein with cu occurs in periplasm

Answer 23

CucA

Question 24

Why does folding of mncA occur in cytoplasm with Mn before it gets transporter to periplasm

Answer 24

Because it traps zinc by folding so cu can’t exchange it