Functions and Dysfunctions of Protein Processing

Question 1

Streptomycin method of action

Answer 1

Binds to 30S subunit and interferes with binding of fmet-tRNA and impairs initiation. Interferes with 30S association with 50S

Question 2

Clindamycin and erythromycin method of action

Answer 2

Binds to large 50S subunit, blocking translocation of the ribosome

Question 3

Tetracycline method of action

Answer 3

Binds to small 30S subunit, blocks entry of aminoacyl-tRNA to ribosomal complex, impairs elongation

Question 4

Chloramphenicol method of action

Answer 4

Inhibits peptidyl transferase activity and impairs peptide bond formation

Question 5

Shiga toxin and ricin method of action

Answer 5

Binds to large 60S subunit (euk.), blocking entry of aminoacyl-tRNA to ribosomal complex

Question 6

Diphtheria toxin method of action

Answer 6

Inactivates GTP bound EF-2, interfering with ribosomal translocation (euk.)

Question 7

Cycloheximide method of action

Answer 7

Inhibits peptidyl transferase (euk.) and impairs peptide bond formation

Question 8

Puromycin method of action

Answer 8

Enters A site and adds to the growing chain

Causes premature chain termination, stops the ribosome from functioning

Question 9

What causes sickle cell anemia

Answer 9

Missense mutation changes GAG to GTG (glutamic acid to valine)
This alters conformation of HbA, causing it to aggregate and form rigid, rod like structures

Question 10

What causes Duchenne muscular dystrophy

Answer 10

Large in frame and out of frame deletions to the dystrophin gene.
OOF deletions result in little/no expression of dystrophin
In frame deletions result in expression of truncated forms of dystrophin, giving rise to milder form of disease called Becker muscular dystrophy

Question 11

Proteins bound for cytosol, mito, nucleus or peroxisomes are translated where

Answer 11

Free ribosomes in cytoplasm

Question 12

Proteins destined for ER, lysosomes, plasma membrane or secretion are translated where

Answer 12

Translation begins on free ribosomes but terminates on ribosomes sent to ER. The proteins have ER targeting sequences present on the first 20 AA residues of the polypeptide

Question 13

What does the nuclear localization signal consist of

Answer 13

Four continuous basic residues- lysine and arginine

Question 14

Properties of secretory pathway ER-targeting signal peptide

Answer 14

1-2 basic AAs (lysine or arginine) near N terminus
Extremely hydrophobic sequence 10-15AAs long on C terminus
SRP binds to ER-targeting signal and ribosome
Translation is halted temporarily, resumed once protein is directed to ER lumen

Question 15

AA signal sequence for ER lumen proteins

Answer 15

KDEL
Lysine
Aspartic acid
Glutamic acid
Leucine

Question 16

Signal for lysosomal proteins

Answer 16

Mannose-6-phosphate

Question 17

Signal for membrane proteins

Answer 17

N terminal apolar sequences

Question 18

Signal for secretory proteins

Answer 18

Tryptophan rich domain

Question 19

I-cell disease

Answer 19

Tagging of lysosomal proteins with M6P is defective
High plasma levels of lysosomal enzymes
Hepatosplenomegaly, recurrent respiratory inf., delayed motor and cognitive skills, abnormal skeletal development, death by 7

Question 20

Which AAs may be modified by acetylation

Answer 20

Lysine

Question 21

Which AAs may be modified by O-glycosylation (OH) and N-glycosylation (CONH2)

Answer 21

O- serine, threonine

N- Asparagine, glutamine

Question 22

Which AAs may be modified by phosphorylation

Answer 22

Serine, tyrosine, threonine, aspartate, histidine

Question 23

Which AAs may be modified by disulfide bond

Answer 23

Cysteine

Question 24

Where in the cell are disulfide bonds added

Answer 24

ER lumen

Question 25

Modifications to AAs in collagen include

Answer 25

Glycosylation and deamination of lysine | Hydroxylation of proline

Question 26

Ascorbic acid and collagen

Answer 26

Ascorbic acid is essential for activity of lysyl and prolyl hydroxylases, which modify lysine and proline in collagen

Question 27

Ehlers-Danlos syndrome

Answer 27

Defect in lysyl hydroxylase | Overly flexible joints; walls of blood vessels, intestines or uterus may rupture

Question 28

Epidermolysis bullosa simplex

Answer 28

Defect in lysyl hydroxylase | Blisters on skin

Question 29

Huntingtons disease

Answer 29

Loss of movement and cognitive functions and psychiatric problems

Question 30

Crutzfeldt-Jacob disease

Answer 30

Failing memory, behavioral changes, lack of coordination and visual disturbances. Late stages involve mental deterioration, blindness, weakness of extremities and coma

Question 31

What causes Alzheimers

Answer 31

Amyloid precursor protein APP breaks down to form amyloid beta peptide Misfolding/aggregation of Ab forms plaques in brain (extracellular) Hyperphosphorylation of Tau (neurofibrillary tangles) are intracellular Mutations in APP and Tau cause familial forms of AD

Question 32

What causes Parkinsons disease

Answer 32

Aggregation of a-synuclein (AS) protein forms insoluble fibrils which deposit as Lewy bodies in dopaminergic neurons in substantia niagra. Mutations in AS cause familial form of Parkinsons

Question 33

What causes huntingtons disease

Answer 33

Mutation in Huntington gene results in expansion of CAG triplet repeats. Results in polyglutamine repeats in abnormal huntington protein. Forms intramolecular H-bonds, which eventually misfold and aggegate -Death of cells in basal ganglia causes symptoms

Question 34

What causes Creutzfeldt-Jakob disease

Answer 34

Caused by misfolding of prion proteins Transmissible- infection by misfolded proteins converts normal proteins to misfolded Belongs to Transmissible spongiform encephalopathies Spongiform- appearance of infected brains, filled with holes and resembles sponges under a microscope

Question 35

Don't forget to look at videos for LOs 1&2 (Key components of protein synthesis and mechanism of translation)

Answer 35

Okee