7.) Precursor Processing

Question 0

Define preprohormone

Answer 0

pre-prohormone, example is insulin. The pre sequence dictates where it will go in the cell, and the pro sequence inactivates the hormone until it is cleaved off.
Contains the signaling peptide and the unprocessed protein.

Question 1

Define pre-hormone

Answer 1

Similar to pre-peptide. It is a hormone that has a sequence that will dictate where it will go in the cell (or out of the cell). Ie it has its signaling peptide sequence.

Question 2

Describe how a protein is signaled to be translocated into the ER lumen.

Answer 2

When peptide is being synthesized, there is an initial ER signal sequence that emerges which will direct the ribosome to a translocator on the ER surface with the help of a SRP (signal recognition peptide). The translocator forms a pore in the ER membrane for the growing peptide. A signal peptidase protein is closely associated with the translocator and will clip the sequence off during translation. The peptide is released into the ER lumen, the ribosome dissociates, and the translocator closes.

Question 3

What are the potential fates for proteins that are synthesized in the cytoplasm?

Answer 3

Remain in the cytoplasm or they are directed to:

The nucleus, mitochondria, plastid, or peroxisome.

Question 4

What are the potential fates for proteins that are synthesized in the endoplasmic reticulum?

Answer 4

Go to the golgi to either be incorporated into the cell membrane, lysosomes, endosomes, or secretory vesicles.

Question 5

Describe how an SRP helps a protein bind to the ER.

Answer 5

Once the signal sequence emerges from the ribosome, an SRP will bind and halt translation. The SRP receptor on the ER membrane, which consists of 2 polypeptide chains, will bind to the SRP and direct the ribosome to the translocator. The SRP and SRP receptor dissociate, and the ribosome will continue with translation.

Question 6

True or False: There are different types of ribosomes that will help to determine whether or not a protein is bound for the cytoplasm or ER.

Answer 6

False: There is only one class of ribosome.

Question 7

What is the key feature that will determine whether or not a protein is synthesized in the ER or in the cytoplasm?

Answer 7

The peptide signal sequence.

Question 8

What is a hydropathy plot, and what kind of data does it measure?

Answer 8

This is a graph that is meant to illustrate the number of hydrophobic and hydrophilic regions of a protein. It is particularly useful for identifying the transmembrane segments of an integral protein.
It is a measure of the free energy change when these particular units are put into an aqueous environment. Therefore, hydrophilic regions will have a much lower free energy change (most likely negative) when compared to hydrophobic regions.

Question 9

What are the necessary features of a signal peptide (aka leader sequence)?

Answer 9

1. ) Ranges in length from 13-36 residues
2. ) Amino terminal portion contains at least one positively charged amino acid residue (Arginine or Lysine)
3. ) Cleavage site is preceded by 4-5 polar residues: positions -1 and -3 have small neutral side chains.

Question 10

True or False: The Signal peptide is always located on the amino terminal end.

Answer 10

False: it is most commonly located on the amino terminal end, but not always.

Question 11

The ER lumen is representative of the _____________ environment

Answer 11

extracellular

Question 12

Where do proteins that are intended to be extracellular get glycosylated?

Answer 12

IN the ER.

Question 13

What residue indicates that a protein needs to be sent to the lysosome?

Answer 13

Mannose-6-phosphate

Question 14

True or False: All cellular membrane proteins are folded in the ER.

Answer 14

True.

Question 15

Proteins that are intended for the membrane will follow the __________ pathway

Answer 15

Constituitive secretory

Question 16

The two types of protein secretory pathways that were mentioned were… (what is the difference between them)

Answer 16

1. ) Constituitive secretory pathway
2. ) Signal mediated diversion to secretory vesicles

Constituitive pathway is unregulated, the other one is regulated, often by binding of a hormone to its receptor.
The constituitive pathway is more likely to be involved with signaling cascades that affect transcription/translation.

Question 17

What is the purpose of N-terminal acetylation? C-terminal amidation?

Answer 17

To prevent degradation by amino peptidases.

To prevent degradation by carboxy peptidases.

Question 18

True or False: Pro-peptide cleavage takes place at pairs of acidic amino acids.

Answer 18

False: Basic amino acids.

Question 19

True or False: A glycine residue at the carboxy terminus always signals for amidation.

Answer 19

True. (slide 28)

Question 20

Define the role of proprotein convertases (PC).

Answer 20

Endopeptidases that cleaves on the carboxy side of basic amino acids (usually pairs of amino acids). First cut usually precludes second cut??

Question 21

Define the role of carboxypeptidase H

Answer 21

Cleaves off carboxy terminated basic amino acids. (lysine and arginine)

Question 22

Define the role of peptidyl-glycine-alpha-monoxygenase (PAM). Where is it located?

Answer 22

These cleave glycine residues in half, leaving behind an amide bond. Substrates are oxygen, vitamin C, and the glycine residue of the peptide to leave behind the amidated peptide, glyoxylate, and a reduced vitamin C.
It is a transmembrane protein in secretory vesicles, with its catalytic activity in the lumen of the vesicle. Typically there is only one copy of this membrane in each vesicle. (note that this type of processing will occur while in transport from the golgi to the plasma membrane, or in the case of neurons from the cell body to locations far away).

Question 23

Define the process of amidating a carboxy terminus .

Answer 23

Endopeptidases named proprotein convertases (PCs) first cleave at basic residues on the carboxy termini. Usually, these amino acids are paired. Then, carboxypeptidase H will cleave these carboxy terminated bases on the N terminus, leaving a glycine residue. Then peptidyl-glycine-alpha-monoxygenase (PAM) will cleave the glycine residue in half leaving an amidated peptide.