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

What occupies the 3’ end of mRNA?

Answer 5

A poly(A) tail.

Question 6

What occupies the 5’ end of mRNA?

Answer 6

7-Methyl Guanosine

Question 7

Sickle Cell Anemia comes from what kind of mutation?

Answer 7

Missense.

Question 8

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

Answer 8

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

Question 9

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

Answer 9

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

Question 10

What gene has deletions in Duchenne Muscular Dystrophy?

Answer 10

The dystropin gene.

Question 11

What terminal region of tRNA binds the amino acid?

Answer 11

The 3’ CCA Terminal Region

Question 12

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

Answer 12

Aminoacyl tRNA Synthetase

Question 13

For Prokaryotic Ribosomes

What is the total Svedberg unit for the entire size?

For the large portion?

For the small portion?

Answer 13

Prokaryotes are 70S total

The large subunit is 50S

The small unit is 30S

Question 14

For Eukaryotic Ribosomes

What is the total Svedberg unit for the entire size?

For the large portion?

For the small portion?

Answer 14

Eukaryotes are 80S total

The large subunit is 60S

The small subunit is 40S

Question 15

In which direction does Translation occur?

Answer 15

5’ to 3’

Same as DNA replication

Question 16

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

Answer 16

AUG, Methionine

Question 17

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

Answer 17

GTP

Question 18

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

Answer 18

Peptidyl Transferase

Question 19

Where does the energy for peptide transfer come from?

Answer 19

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

Question 20

What binds to stop codons?

Answer 20

Release Factors

(Not any tRNA / amino acid)

Question 21

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

Answer 21

Ester Bond

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

Question 22

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

Answer 22

GTP

Question 23

In which subunit does peptidyl transferase activity occur?

Answer 23

The large subunit, for both prokaryotes and eukaryotes.

Question 24

For Streptomycin:

Does it affect Prokaryotes or Eukaryotes?

Where does it bind?

What does it disrupt?

Answer 24

It affects prokaryotes

It binds to the 30S subunit

It disrupts initiation of translation via binding formylmethionine-tRNA

Question 25

For **Shiga Toxin and Ricin**: Does it affect Prokaryotes or Eukaryotes? Where does it bind? What does it disrupt?

Answer 25

It affects **Eukaryotes** It binds to the **60S** subunit Disrupts elongation

Question 26

For **Clindamycin and Erythromycin**: Does it affect Prokaryotes or Eukaryotes? Where does it bind? What does it disrupt?

Answer 26

It affects **prokaryotes** It binds to the **50S** subunit It disrupts **translocation of the ribosome** *Clinda with the fat _red_ (erythromycin) face yells at the 50 ribosomes to stop running.*

Question 27

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

Answer 27

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

Question 28

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

Answer 28

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

Question 29

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

Answer 29

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

Question 30

What does **Puromycin** cause?

Answer 30

Premature chain release, which stops the ribosome.

Question 31

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

Answer 31

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

Question 32

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

Answer 32

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

Question 33

What feature of amino acids determine sorting into the **cytoplasm**?

Answer 33

A lack of sorting signal altogether.

Question 34

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

Answer 34

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

Question 35

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

Answer 35

**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 36

What signal determines transport into the peroxisomes?

Answer 36

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

Question 37

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

Answer 37

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 38

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

Answer 38

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 39

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

Answer 39

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

Question 40

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

Answer 40

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

Question 41

What signal determines a protien be sent to a lysosome?

Answer 41

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

Question 42

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

Answer 42

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

Question 43

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

Answer 43

**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 44

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

Answer 44

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 45

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

Answer 45

Cystine

Question 46

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

Answer 46

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

Question 47

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

Answer 47

**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 48

What residues are targets for Phosphorylation?

Answer 48

**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 49

What two camps are there for the etiology of Alzheimers Disease

Answer 49

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 50

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

Answer 50

Mutations in APP and Tau Brain aging. :(

Question 51

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

Answer 51

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

Question 52

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

Answer 52

Mutations in alpha-synuclein Brain aging

Question 53

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

Answer 53

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

Question 54

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

Answer 54

**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