Translation and Protein Processing Flashcards
1
Q
Purpose of Kozak sequence in mRNA strand?
A
Ribosomal binding during translation
2
Q
Subunits of eukaryotic 80S ribosome?
A
60S and 40S subunits
3
Q
Proteins assoc w/ polyribosomes on RER surface are cotranslated where?
A
Thru RER membrane into ER lumen
4
Q
What marks start of translation initiation?
A
mRNA binds 40S ribosomal subunit
5
Q
What marks start of elongation?
A
60S subunit binds to complex and forms active ribosome
6
Q
Function of eIF2?
A
Facilitates binding of initiating Met-tRNA(Met) to 40S subunit
7
Q
Functions of eIF3? (2)
A
- First factor to bind 40S subunit
- facilitates subsequent steps
8
Q
Functions of eIF4A? (2)
A
- RNA helicase activity removes secondary structure in mRNA to permit binding to 40S subunit
- part of eIF4F complex
9
Q
Functions of eIF4B? (2)
A
- binds to mRNA
- facilitates scanning of mRNA to locate first AUG
10
Q
Cause of CNS Hypomyelination and Vanishing White Matter (VWM)?
A
Missense mutation in eIF2
11
Q
Direct effort of VWM?
A
Decreased expression/function of eIF2
12
Q
Mechanism of VWM and fever? (4)
A
- translation often stalled in response to stress (eg fever)
- eIF2 prevents accumulation of misfolded proteins by preventing translation during fever
- eIF2 mutation impairs this ability
- abnormal folded proteins build up and affect glial cells –> loss of myelin sheath
13
Q
Mechanism of tetracycline?
A
- bacterial antibiotic
- inhibits binding of aminoacyl-tRNA @ A-site
14
Q
Mechanism of chloramphenicol?
A
- bacterial antibiotic
- inhibits peptide bond formation by Peptidyltransferase
15
Q
What powers translocation?
A
GTP hydrolysis bound to eEF-2 translocase
16
Q
What bacterial antibiotic inhibits translocation?
A
Erythromycin
17
Q
Functions of eIF3 and eIF6?
A
- eIF3 binds inactive 40S subunit until next intitiation
- eIF6 binds 60S subunit
18
Q
Functions of Streptomycin? (2)
A
- prevents transition from initiation complex to chain elongation
- causes miscoding
19
Q
Function of Rifamycin?
A
- blocks transc initiation by binding RNA Pol
20
Q
Function of heat shock proteins?
A
- prevent inappropriate hydrophobic aggregations b/w nearby AAs
21
Q
Function of Peptidyl Prolyl cis-trans Isomerase?
A
- converts Pro res from trans to cis config
- cis-Proline can form hairpin beta-turns
22
Q
Function of Protein Disulfide Isomerase (PDI)?
A
- breaks inappropriate disulfide bonds until correct ones are formed
23
Q
How are Amyloidoses formed? (2)
A
- exposed beta-sheets form aggregate w/ similarly misfolded beta-sheets –> amyloid fibrils
- fibrils further assemble into insoluble Amyloidoses
24
Q
Mechanism of Alzheimers? (4)
A
- Amyloid Precursor Protein (APP) should be alpha-helical
- APP proteolytic cleavage –> misfolding into beta sheets
- beta sheets aggregate thru Phe interactions
- beta amyloid plaques form in extracell space
25
Role of amyloid formation in Type II diabetes? (3)
- improper folding of Islet Amyloid Polypeptide (IAPP, Amylin)
- apoptosis of pancreatic beta islet cells
- reduced amylin and insulin levels
26
Role of amyloid formation in Huntigton's disease? (4)
- misfolding of Huntingtin (HTT) protein --> aggregates
- HTT has 5'-CAG-3' tri-nt repeats that code for polyQ res chain
- more than 40 res --> full disease penetrance
- mutant HTT cleaved and yields amyloid aggregates that interfere w/ NT release
27
Role of amyloid formation in Parkinson's disease? (2)
- aggregates from misfolding of alpha synuclein (Lewy bodies)
- results in death of dopaminergic neurons
28
Role of amyloid formation in Amyotrophic Lateral Sclerosis (ALS, Lou Gehrig's disease)? (2)
- affects motor neurons
- Superoxide dismutase protein (SOD1) becomes misfolded --> aggregates
- only accts for a small fraction of ALS cases
29
Role of amyloid formation in Spinal cerebellar ataxia? (3)
- Ataxin protein has CAG tri-nt repeats
- promotes stretch of PolyQ res
- also non-polyQ mediated mechanisms
30
What enzymes cleave APP to produce PM protein? (2)
1. alpha secretase cleaves APP in extracell domain
2. gamma secretase (Presenelin, PSEN1) cleaves APP in intracell domain
- leaves non-harmful 26 res peptide embedded in PM
31
Discuss dvp'ment of beta amyloid plaque (3)
- beta secretase cleaves APP in a diff extracell location
- generates 42 res peptide (AB42)
- has more beta strand structure that misfolds and aggregates
32
Characteristics of Familial Alzheimer's disease (FAD)? (2)
- early onset of symptoms and accelerated progression
| - mutation w/i APP seq that cluster near AB42 and enchance proteolysis --> more AB42 production
33
Genetic components of late onset Alzheimer's disease? (5)
- involves Apolipoprotein E (ApoE)
- involved in transprt of cholesterol- and TGC-carrying complexes in blood
- homozygous E4/E4 ind's have higher risk for Alzheimer's
- homozygous E2/E2 may be protective for Alzheimer's
- E3 allele has no seen effect
34
Clinical importance of acylation? (2)
- occurs b/w palmitate or myristate and proteins on cytosolic leaflet of PM
- Src (proto-oncogene kinase) becomes oncogenic after acylation
35
Clinical importance of prenylation? (4)
- occurs b/w unsat FA farnesyl or geranylgeranyl and proteins on C-leaflet of PM
- Ras proto-oncogene is prenylated normally
- loss of prenylation --> decrease in Ras oncogenic transformation
- cancer drugs inhibit Ras prenylation
36
Clinical importance of GPI-linked proteins? (3)
- covalenty bound to phospholipid phosphatidylinositol via series of intervening carbs
- assoc w/ E-leaflet of PM
- involved in blood coagulation cascade
37
How is acetylation used for (acetylsalicylic acid) Aspirin delivery?
- it makes molec's more permeable to blood-brain barrier (BBB)
38
What important signaling molec is tri-methylated?
Calmodulin
39
Mechanism of blood clotting factor Prothrombin? (2)
- contains gamma-CarboxyGlu res for neg charge
| - neg charge helps it effectively bind Ca2+
40
What does a Prothrombin time (PT) measure?
Blood coagulation
41
Explain why breast milk supplies AA, phosphate, and Ca2+? (2)
- casein is main milk protein
| - contains many phosphoserine res that bind Ca2+
42
Describe insulin cleavage (4)
- PreProinsulin has its N' end cleaved in ER
- disulfide bonds formed in oxidizing env of ER --> Proinsulin
- internal C-peptide cleaved off Proinsulin
- A chain and B chain held together by disulfide bonds --> final insulin protein
43
What is precursor peptide for several peptide NTs?
Propiomelanocortin (POMC)
44
Components of holoenzyme? (2)
- active enzyme
| - coenzyme prosthetic group
45
What is an apozyme (apoprotein)?
Inactive enzyme w/o its prosthetic group
46
What peptide res receives Ub tag?
Lysine
47
Enzyme that does Ub taggin?
Ub-ligase
48
Where do polyubiquinated proteins go?
26S proteasome complex
49
Composition of ricin? (2)
1. B chain w/ galactose binding chains that allows cell entry thru H-bonding
2. A chain = active site that depurinates adenine bases w/i rRNA
50
Mechanism of ricin poisoning? (3)
- depurinates adenine bases w/i 28S rRNA
- depurinated 28S rRNA targeted for degradation
- inhibits translation
51
Most important posttranscriptional modification of tRNA?
Addition of CCA seq to 3' end of molec
