1.7: Regulation of the Proteome Flashcards
what do prokaryotes and eukaryotes use translational control mechanisms to regulate protein expression in response to
stressful situations
explain the method of translational regulation in prokaryotes
mRNAs have 6 nucleotide shine dalgarno (sd) sequences upstream of the AUG start codon (it’s inside the 5’ UTR) - it correctly positions AUG in the ribosome and provides translational control mechanisms
state and define the 4 mechanisms of translational regulation in prokaryotes
1: a specific rna binding protein blocks access to the sd sequence = no translation = no protein
2: temperature regulated rna structures – usually stem-loop structure to block access to sd and increased temperature opens it up
3: riboswitch (eg s-adenosyl methionine): small molecule causes structural rearrangement of rna blocking sd
4: antisense rna (eg iron storage proteins): antisense rna produced elsewhere in the genome base pairs w mRNA and blocks sd
what process are sd sequences needed for
translation in prokaryotes
do prokaryotes and eukaryotes have SIMILAR translational regulation mechs
yes
what does aconitase do
translational repressors can bind near initiator aug and inhibit translation in eukaryotes
ferritin binds iron and releases it in a controlled manner - ferritin isn’t needed when iron is low so aconitase binds to the ferritin rna near the start site and blocks translation - when iron is in excess, aconitase binds iron, there is a conformatonal change in aconitase, and ferritin rna is released
what other receptor does aconitase regulate, apart from ferritin
transferrin
in eukaryotes, what interferes w 5’ cap and 3’ poly a tail interactions that are required for efficient translation
repressor proteins
t/f can miRNAs regulate EUKARYOTIC translation
true
describe the regulation of eukaryotic initiation factors (long answer)
- eIF2 (very important) forms a complex w GTP and recruits the initiator tRNA (methionyl) to the small ribosomal subunit <– binds the 5’ end of mRNA and scans for the first AUG
- when found first AUG, eIF2 hydrolyzes gtp to gdp
- gtp hydrolysis causes a conformational change in eIF2
- eIF2 bound to gdp is released and is inactive
- reactivation of eIF2 requires eIF2B which is a guanine nucleotide exchange factor (GEF) - means it causes the exchange of gdp for gtp
which initiation factor is crucial in translation initiation
eIF2
does gef cause phosphorylation in eukaryotic translation initiation
no! it is an exchange of gdp to gtp
what are reactivation of eIF2 require in eukaryotic translation initiation
eIF2b
what modification regulated eIF2 REACTIVATION
phosphorylation - phosphorylated eIF2 sequesters eIF2B as an inactive complex
which is more abundant in cells eIF2 or eIF2B
eIF2
are all mRNAs equally affected by eIF2 phosphorylation and why
no, there is a different mechanism for a couple of important proteins
what happens when eIF2B is all sequestered by eIF2
translation is dramatically reduced
can you reverse the inactivation of eIF2B
yes, just dephosphorylate it
list the steps that protein must undergo to become functional
- proteins must fold properly to adopt their 3d structure
- proteins are covalently modified w chemical groups (eg sugars, phosphate)
- proteins interact w other proteins and small molecules (cofactors)
*typical order but doesn’t have to be like this
hydrophobic aa are buried in the ________________
interior core
t/f for some proteins, folding begins as they emerge from ribosomes but some are completely folded after synthesis
t
most proteins require a special class of proteins called? for proper folding
chaperones
why are many chaperones called heat-shock proteins (hsp)
they are synthesized to high amounts by cells at elevated temperatures
will you only see heat shock proteins at high temp
no
what hsps make up chaperonin
hsp70 and hsp60
list 3 commonalities between hsp70 and hsp60
both assist protein folding, interact w exposed hydrophobic residues of misfolded proteins and both use energy from atp hydrolysis to promote proper folding
can both hsp complexes function at the same time
no -
why do chaperone proteins function like an isolation chamber
they need atp to get the GroES cap, keep the protein in there to give it time to fold, use atp to take the cap out
improperly folded proteins can ________ and become toxic to cells
aggregate
what enzyme monitors improperly folded proteins and how does it work
proteasome, it degrades proteins by using exposed hydrophobic residues to mark proteins for degradation
what do chaperons and proteasomes compete for
misfolded proteins
the _______ time to fold, the higher the chance of being degraded
longer
How many of the following statements are correct?
i. Treatment of cells with HSP inhibitors should result in a decrease in protein
degradation.
ii. Treatment of cells with an iron chelator (which removes excess cellular iron)
should result in a decrease in ferritin transcription.
iii. Treatment of cells with a miRNA complementary to eIF2B should result in
an increase in transcription.
a. 0
b. 1
c. 2
d. 3
a. 0
i is wrong is it should increase protein degradation
ii is wrong bc it decreases ferritin translation, not transcription
iii is wrong bc it should lead to a decrease in translation
