2. Functions and Dysfunction of Protein Processing

Question 1

What is a Missense mutation?

Answer 1

A mutation that changes a single amino acid. May do nothing, or change the protien entirely.

Question 2

What is a Nonsense mutation?

Answer 2

A mutation that changes a codon into a stop codon.

(This is also caused a null mutation)

You think you can stop? Nonsense!

Question 3

What is a Frameshift mutation?

Answer 3

When a nucleotide is deleted or added, causing all the others to be wrong.

Like when you accidentally skip a bubble on a scantron and get a 3% on a test

Question 4

What is a silent mutation?

Answer 4

A mutation that does not change the resulting amino acid sequence.

Question 5

Sickle Cell Anemia comes from what kind of mutation?

Answer 5

Missense.

Question 6

In Sickle Cell Anemia, what amino acid is substituted for which other amino acid?

Answer 6

Glutamate (Negative charge and Hydrophillic) becomes Valine (hydrophobic)

Question 7

In Duchenne’s Muscular Dystrophy - what sort of mutation is found?

Answer 7

Frame shift due to deletion, either out of frame (Severe) or in-frame (less severe)

Question 8

What gene has deletions in Duchenne Muscular Dystrophy?

Answer 8

The dystropin gene.

Question 9

What terminal region of tRNA binds the amino acid?

Answer 9

The 3’ CCA Terminal Region

Question 10

What enzyme serves to “activate” an Amino Acid to tRNA, and helps to ensure the fidelity of the genetic code?

Answer 10

Aminoacyl tRNA Synthetase

Question 11

For Prokaryotic Ribosomes

What is the total Svedberg unit for the entire size?

For the large portion?

For the small portion?

Answer 11

Prokaryotes are 70S total

The large subunit is 50S

The small unit is 30S

Question 12

For Eukaryotic Ribosomes

What is the total Svedberg unit for the entire size?

For the large portion?

For the small portion?

Answer 12

Eukaryotes are 80S total

The large subunit is 60S

The small subunit is 40S

Question 13

In which direction does Translation occur?

Answer 13

5’ to 3’

Same as DNA replication

Question 14

What is the initiation codon, and what does it code for?

Answer 14

AUG, Methionine

Question 15

What high energy compound is hydrolysed to help with loading of aminoacyl tRNA?

Answer 15

GTP

Question 16

What enzyme attaches the second peptide to the first, releasing it from the tRNA?

Answer 16

Peptidyl Transferase

Question 17

Where does the energy for peptide transfer come from?

Answer 17

From the high energy bond between the amino acid and tRNA.

Question 18

What binds to stop codons?

Answer 18

Release Factors

(Not any tRNA / amino acid)

Question 19

What sort of bond is cleaved by release factor, and where is it located?

Answer 19

Ester Bond

Between the C terminus of the polypeptide and the tRNA’s CCA terminal region.

Question 20

When all is said and done, what dissociates the entire ribosomal complex?

Answer 20

GTP

Question 21

In which subunit does peptidyl transferase activity occur?

Answer 21

The large subunit, for both prokaryotes and eukaryotes.

Question 22

For Streptomycin:

Does it affect Prokaryotes or Eukaryotes?

Where does it bind?

What does it disrupt?

Answer 22

It affects prokaryotes

It binds to the 30S subunit

It disrupts initiation of translation via binding formylmethionine-tRNA

Question 23

For Shiga Toxin and Ricin:

Does it affect Prokaryotes or Eukaryotes?

Where does it bind?

What does it disrupt?

Answer 23

It affects Eukaryotes

It binds to the 60S subunit

Disrupts elongation

Question 24

For Clindamycin and Erythromycin:

Does it affect Prokaryotes or Eukaryotes?

Where does it bind?

What does it disrupt?

Answer 24

It affects prokaryotes

It binds to the 50S subunit

It disrupts translocation of the ribosome

Question 25

For **Tetracyclines**: Does it affect Prokaryotes or Eukaryotes? Where does it bind? What does it disrupt?

Answer 25

It affects **prokaryotes** It binds to the **30S** subunit It disrupts **elongation**

Question 26

For **Chloramphenicol**: Does it affect Prokaryotes or Eukaryotes? What does it disrupt?

Answer 26

It affects **both** Prokaryotes and Eukaryotes It inhibits prokaryotic / eukaryotic peptidyl transferase

Question 27

For **Cycloheximide**: Does it affect Prokaryotes or Eukaryotes? What does it disrupt?

Answer 27

It affects **eukaryotes** It disrupts **peptidyl transferase**

Question 28

What does **Puromycin** cause?

Answer 28

Premature chain release, which stops the ribosome.

Question 29

Where does the **cytoplasmic pathway** send protiens? (4 places)

Answer 29

1. Cytosol 2. Mitochondria 3. Nucleus 4. Peroxisomes

Question 30

Where does the **secretory pathway** send protiens?

Answer 30

1. Endoplasmic Reticulum 2. Lysosomes 3. Plasma Membranes 4. Secretion ## Footnote *(All of these are secretion / vesicle related places)*

Question 31

What feature of amino acids determine sorting into the cytoplasm?

Answer 31

A lack of sorting signal altogether.

Question 32

What signal sorts amino acids into the **mitochondria**?

Answer 32

**N-Terminal Hydrophobic alpha-helix** (no + charges) ## Footnote *Imagine a cork shaped mitochondria, and the N terminal alpha helix is a corkscrew*

Question 33

What signal sorts into the Nucleus? (Nuclear Localization Signal)

Answer 33

**Lysine** and **Arginine** rich ends (four in a row) ## Footnote * The Nucleus is invaded by _lying pirate_ protiens (Lys and Arrrrg)* * (But once the pirates get up to the membrane, they get scared and need chaperones)*

Question 34

What signal determines transport into the perosixomes?

Answer 34

**-SKL** *Surviving around all that peroxide takes _SKL_ (skill)*

Question 35

What region determines protien ER entrance, and is common to every member of the secretory pathway? (ER Targeting Signal)

Answer 35

A positively charged alpha-helix ## Footnote *The protiens of the secretory pathway all start out feeling _positive_ about their prospects. They're going places! (Secretion)*

Question 36

What sequence causes an amino acid to be held in the ER? (ER retention sequence)

Answer 36

KDEL (Lysine Aspartate Glutamate Leucine) ## Footnote ***_Leu_**is **_Ly_**ed about an _Asp_ biting his _Glut_, and got to stay in the ER and eat ice cream.*

Question 37

Out of the protiens sorted to the secretory pathway, which ones go through the golgi apparatus?

Answer 37

**Lysosomal**, **cell** **membrane**, and **secretory vesicle** protiens

Question 38

What signal determines transport of a protien into the cell membrane?

Answer 38

A **Stop Transfer** sequence ## Footnote *Stop transfering me around the golgi apparatus and stick me in the membrane already!*

Question 39

What signal determines a protien be sent to a lysosome?

Answer 39

Mannose 6-Phosphate *A lysosome is a trash-_mann_*

Question 40

What signal determines a protien be sent from the golgi body to a secretory vesicle?

Answer 40

A **tryptophan** rich domain ## Footnote *The protien didn't want to leave the cell, but it _tripped_ (tryptophan) into the secretory vesicle.*

Question 41

What **protien** assists a nascent polypeptide get into the ER? How does it do this?

Answer 41

**SRP** (Signal Recognition Particle) SRP hugs the ribosome, checks for the positively charged helix, and then binds to SRP-receptor protien in the ER membrane. It does this to bring the ribosome-polypeptide close to an ER membrane protien translocator.

Question 42

What is defective in I-Cell Disease? (aka Inclusion Cell Disease) What happens as a result?

Answer 42

Mannose 6 phosphate Protiens back up and lysosomes don't work. ``` *The inclusions of stuff inside the lysosomes that aren't being broken down are the "inclusions" that give the disease its name. #DarrenFacts* ```

Question 43

Oxidation of which amino acids can result in a di-sulfide bond?

Answer 43

Cystine

Question 44

What residues can be affected by **Acetylation**?

Answer 44

**Lysine** *Lysine has the amine group at the end that makes a convenient target for acetylation.*

Question 45

What residues can be affected by Glycosylation? Which ones are O-glycosylation targets? Which ones are N-glycosylation targets?

Answer 45

**Serine, Threonine, Asparagine, Glutamine** O-glycosylation: **Serine, Threonine** *(They have the OH)* N-Glycosylation: **Asparagine, Glutamine** (They have the -CONH₂) * I'm Serious,There are Assassins, Glen!* * (Sugar-high induced paranoid delusions)*

Question 46

What residues are targets for Phosphorylation?

Answer 46

**Serine Threonine Tyrosine** * Searing Three Tires* * (Amino acids hate phosphates, so these Three kinases really Sear their Tires)* Note: I find no evidence of relevant phosphorylation of Histidine or Aspartate residues anywhere, but it's on the table so it goes in the last priority learning slot for me.

Question 47

What two camps are there for the etiology of Alzheimers Disease

Answer 47

1. APP to **Amyloid Beta Peptide** which forms **plaques** 2. **Hyperphosphorylation of Tau,** which prevents it from doing its job of stabalizing microtubules, causing neurofibrillary tangles.

Question 48

What causes familial Alzheimers? What is the common factor for sporadic Alzheimers?

Answer 48

Mutations in APP and Tau Brain aging. :(

Question 49

What is the etiology of Parkinsons? _{Hint: Protein, deposit, location} What causes the symptoms?

Answer 49

Aggregation of **alpha-synuclein (AS)** protien depositing as fibrils in the **Lewy bodies** of the **Substantia Nigra** Reduced availability of **dopamine**

Question 50

What causes familial Parkinsons? What is the common denominator for the sporadic form?

Answer 50

Mutations in alpha-synuclein Brain aging

Question 51

What leads to Huntington's disease? What does this cause physiologically? What causes the symptoms?

Answer 51

Mutation in **Huntington Gene** leads to a bunch **CAG** repeats **Polyglutamine repeats** lead to misfolding and aggregations of the HTT (Huntington) protien **Selective cell death,** speciffically in the **basal ganglia**.

Question 52

What disease is characterized by infection with, or spontanious generation of, a scrapie version of the prion protein?

Answer 52

**Creutzfeldt-Jacob Disease (CJD)** (Note: The word Scrapie is a classical name for a similar disease in sheep, thought to be caused by a misfolded prion protien) #DarrenFacts