Lecture 2: Protein Processing

Question 1

What does streptomycin inhibit?

Answer 1

Binds to 30s subunit and interferes with binding of fmet-tRNA
-Impairs initiation

Question 2

What doe clindamycin and erythromycin inhibit?

Answer 2

Binds to 50s subunit

-blocks translocation of ribosome

Question 3

What does tetracycline inhibit?

Answer 3

Binds to 30s subunit and blocks entry of aminoacyl-tRNA to ribosomal complex
-impairs elongation

Question 4

What does chloramphenicol inhibit?

Answer 4

Inhibits peptidyl transferase activity and impairs peptide bond formation in prokaryotes

Question 5

How do Shiga toxin and ricin work?

Answer 5

Binds to 60s subunit and blocks entry of aminoacyl-tRNA to ribosomal complex

Question 6

How does Diphtheria toxin work?

Answer 6

Inactivates GTP-bound elongation factor-2

-Impairs ribosomal translocation

Question 7

How does cycloheximide work?

Answer 7

Inhibits peptidyl transferase activity and impairs peptide bond formation in eukaryotes

Question 8

How does puromycin work?

Answer 8

Premature chain termination in both prokaryotes and eukaryotes

Question 9

What is the pathology behind Sickle Cell Disease?

Answer 9

Missense mutation

Glutamic Acid –> Valine

Question 10

What is the pathology behind Duchenne Muscular Dystrophy?

Answer 10

Frameshift mutation that leads to dysfunctional dystrophin protein in males
*muscle wasting

Question 11

In the cytoplasmic pathway, where are proteins destined for?

Answer 11

Cytoplasm
Mitochondria
Nucleus
Peroxisomes

Question 12

In the secretory pathway, where are proteins destined for?

Answer 12

Plasma Membrane
Lysosomes
Endoplasmic Reticulum

They have ER targeting signal peptide and undergo post-translational modification in ER/Golgi

Question 13

What is the signal for a protein sent to the cytoplasm?

Answer 13

None

Question 14

What is the signal for a protein sent to the mitochondria?

Answer 14

N-terminal hydrophobic alpha helix signal peptide

-recognized by TIM and TOM transporters in mitochondria

Question 15

What is the signal for a protein sent to the nucleus?

Answer 15

KKKRK signal (lysine/arginine rich)

• imported via nuclear pores
• large proteins require nuclear localization signals

Question 16

What is the signal for a protein sent to peroxisomes?

Answer 16

C-terminal SKL signal sequence

Question 17

What is the signal for a protein sent to the ER Lumen?

Answer 17

C-terminal KDEL retention signal

Question 18

What is the signal for a protein sent to the lysosomes?

Answer 18

Mannose 6-phosphate signal group

Question 19

What is the signal for a protein sent out for secretion?

Answer 19

Tryptophan rich domain

Question 20

What is the signal for a protein sent to the membranes?

Answer 20

N-terminal apolar region (stop transfer sequence)

Question 21

What is glycosylation?

Answer 21

Proteins are covalently linked to sugar residue in ER lumen

O-glycosides: Hydroxyl groups on Ser or Thr residues
N-glycosides: Acid-amide group on Asparagine

Question 22

What is phosphorylation?

Answer 22

Formation of ester bond between phosphate and OH group of amino acid
-Ser/Thr Activity or Tyrosine Kinase

Question 23

What are disulfide bond formations?

Answer 23

Disulfide bonds stabilize proteins
Bonds between Thiol (SH) groups of 2 cysteine residues

Formation in ER lumen

Question 24

Acetylation

Answer 24

Acetyl added on lysine residues

-important for protein modification

Question 25

What is essential for the activity of lysyl and prolyl hydroxylases?

Answer 25

Ascorbic Acid

Question 26

Defects in in lysyl hydroxylases can result in?

Answer 26

Skin, bone, joint disorders * Ehlers-Danlos Syndrome * Nevo Syndrome * Bruck Syndrome

Question 27

What is the pathology behind Alzheimer's Disease?

Answer 27

Amyloid precursor protein breaks down to form Amyloid Beta Peptide (AB) - misfolding and aggregation in brain - Hyperphosphorylation of Tau

Question 28

What is the pathology behind Parkinson's Disease?

Answer 28

Aggregation of alpha-synuclein protein - Deposits as Lewy bodies in dopaminergic neurons in substantia nigra - Reduced availability of dopamine

Question 29

What is the pathology behind Huntington's Disease?

Answer 29

Mutation in huntingtin gene --> expansion in CAG triplets | -abnormal polyglutamine repeats

Question 30

What is the pathology behind Creutzfeldt-Jakob Disease?

Answer 30

AKA Mad Cow Disease/Encephalopathy - misfolding due to prion proteisn - infection - spongy brain