Lecture 11: Functions and Dysfuction of Protein Processing

Question 1

Streptomycin

Answer 1

• prokaryotic 30s subunit binding

- interferes w/fmet-tRNA bindings and 50s association

Question 2

Clindamycin and erythromycin

Answer 2

• prokaryotic 50s subunit binding

- blocks translocation of ribosome

Question 3

Tetracycline

Answer 3

• prokaryotic 30s subunit binding
• blocks aminoacyl-tRNA to ribosomal complex
• blocks ELONGATION

Question 4

Chloramphenicol

Answer 4

• prokaryotic inhibitor

- inhibits peptidyl transferase, impairs peptide bond formation

Question 5

Shiga toxin and Ricin

Answer 5

• eukaryotic 60s subunit binding

- blocks aminoacyl-tRNA

Question 6

Diphtheria toxin

Answer 6

• eukaryotic inhibitor
• inactivates GTP-bound EF-2
• blocks ribosomal translocation

Question 7

Cycloheximide

Answer 7

• eukaryotic inhibitor
• inhibits peptidyl transferase
• impairs peptide bond formation

Question 8

Puromycin

Answer 8

• eukaryotic/prokaryotic
• causes premature chain termination
• enters A site, forms puromycylated (premature chain release)
• hydrolysis resistant (stops ribosome function)

Question 9

Silent Mutations, Missense Mutations, Nonsense Mutations, Frameshift Mutations

Answer 9

Silent - does not change amino acid

Missense - changes amino acid in protein (no effect or vastly different effect)

Nonsense - codon changes into stop codon (truncated)

Frameshift - OOF (change codon sequence, alteration in AA sequence of protein)

Question 10

Sickle Cell Anemia

Answer 10

• missense (6th codon in allele of Beta-globin)
• glutamic acid changed to valine (hydrophilic to hydrophobic)
• poor oxygen capacity and tend to clog capillaries (deformed RBCs)

Question 11

Duchenne Muscular Dystrophy

Answer 11

• frameshift (dystrophin gene deletions)
• little (Becker) or no (Duchenne) dystrophin protein
• muscle wasting

Question 12

Cytoplasmic and Secretory proteins go where?

Answer 12

Cytoplasmic: cytosol, mitochondria, nucleus, peroxisomes (begin/end on free ribosome)

Secretory: ER, lysosomes, plasma membranes, secretion (begins free ribosome, sent to ER)

Question 13

Mitochondria Translocation Signal

Answer 13

N-terminal hydrophobic alpha-helix signal peptide

Question 14

Nucleus Translocation Signal

Answer 14

Lysine/Arginine rich (KKKRK)

Question 15

Peroxisome Translocation Signal

Answer 15

Serine/Lysine/Leucine (SKL)

Question 16

ER Lumen Translocation Signal

Answer 16

Lysine/Aspartate/Glutamine/Leucine (KDEL)

Question 17

Secretory Vesicle Translocation Signal

Answer 17

Trp-rich domain (Tryptophan)

Question 18

Lysosome Translocation Signal

Answer 18

Mann 6-P

Question 19

Cell Membrane Translocation Signal

Answer 19

N Terminal apolar

Question 20

Signal Recognition Particle (SRP) action

Answer 20

• wraps around ribosome-mRNA-peptide complex (ER tethering)
• complex has 1-2 basic AA and 10-15 hydrophobic sequence
• enzymes on lumen side cleave protein to release

Question 21

I Cell Disease

Answer 21

• lysosomal proteins are mannose 6P deficient (not sent to lysosomes)
• high plasma lvls of lysosomal enzymes
• failure to thrive, developmental delays, physical manifestations

Question 22

What does Acetylation do and what AA does it affect?

Answer 22

• covalently attaches amine group
• works on Lys
• use acetyl CoA as donor

Question 23

What does Glycosylation do and what AAs does it affect?

Answer 23

• adds sugar groups
• O-glycosylation: Serine, Threonine
• N-glycosylation: Asparagine, Glutamine

Question 24

What does Phosphorylation do and what AAs does it affect?

Answer 24

• phosphate linked by esterfication

- Ser, Tyr, Thr, Asp, His

Question 25

What do Disulfide bonds do and what AA does it affect?

Answer 25

- covalent linkage of cysteine residues (via -SH) | - Cysteine

Question 26

Post Translational Modifications of Collagen

Answer 26

- modifications important for assembly of collagen - ascorbic acid essential for activity for lysyl and prolyl hydroxylases - defect in lysyl hydroxylases result in disorders

Question 27

Alzheimer's Disease (AD)

Answer 27

- form amyloid beta peptide - forms plaques (extracellular) and hyperphosphorylation of Tau (intracellular) --> tangles - APP and Tau mutations cause familial AD - brain aging causes sproadic form

Question 28

Parkinson's Disease (PD)

Answer 28

- aggregation alpha-synuclein forms insoluble fibrils (Lewy bodies) in dopaminergic neurons in substantia nigra - symptoms due to reduced availability of dopamine - Mutations (familial form), brain aging (sporadic)

Question 29

Huntington's Disease (HD)

Answer 29

- Huntingtin gene mutation = CAG triplet repeats - forms Polyglutamine repeats (misfold and aggregate) - selective death of basal ganglia cells (symptoms)

Question 30

Creutzfeldt-Jakob Disease

Answer 30

- misfolding of prion proteins - transmissible: misfolded proteins convert proteins to misfold - transmissible spongiform encephalopathies