Protein folding, processing and sorting

Question 1

Where are polypeptide chains synthesised?

Answer 1

In the ribosome tunnel

Question 2

How many amino acids can fit inside the tunnel in a human ribosome?

Answer 2

~20

Question 3

What arrangement does the polypeptide chain form in the ribosome tunnel? What happens when it leaves the tunnel?

Answer 3

In a linear format inside the tunnel (due to space constraints)
Once out of the tunnel it immediately folds

Question 4

Why does the amino acid fold over once it leaves the ribosome tunnel?

Answer 4

It goes from a non-polar environment inside the ribosome to a polar environment in the cytoplasm therefore tries to re-arrenge itself so that the non-polar side chains are on the inside and the polar side chains on the outside

Question 5

What shapes can the polypeptide chain fold into to optimise its arrangement in the polar environment?

Answer 5

α helix (coil) or a ß sheet (primary chain zig zags forming a pleat sheet)

Question 6

How are the α helix and ß sheets stabilised?

Answer 6

By hydrogen bonds

Question 7

What kind of structure are α helix and ß sheets?

Answer 7

Secondary structures

Question 8

What side chains makes amino acids non-polar? What is on these side chains that makes them non-polar? How does this impact their response in the polar environment of the cytoplasm?

Answer 8

R group
H, CH3 or multiple bonded CH2+
Causes this group to be hydrophobic

Question 9

What side chains makes amino acids polar? What is on these side chains that makes them polar? How does this impact their response in the polar environment of the cytoplasm?

Answer 9

R group
OH-, SH or an amide ( -C=O,NH2)
Causes this group to be hydrophilic

Question 10

What side chains makes amino acids electrically charged? What is on these side chains that makes them electrically charged? How does this impact their response in the polar environment of the cytoplasm?

Answer 10

R group
Acidic or basic groups
Acid = carboxyl group (COO-), basic = amino group

Question 11

What kind of structure do secondary structures get turned into?

Answer 11

Tertiary structures

Question 12

How are tertiary structures made?

Answer 12

Secondary structures are folded over by other proteins

Question 13

What are the forces involved in holding the shape of a tertiary structure? What parts of the protein do they bond? Are these weak or strong?

Answer 13

Hydrophobic collapse (poorly understood force…)
Van Der Waals forces between non-polar amino acid side chains (weak)
Hydrogen bonds between polar amino acid side chains (strong)
Ionic bonds between charged amino acid side chains (weak)
Disulphide bridges between cysteine molecules (strong - is covalent FYI)

Question 14

What is the shape of a tertiary structure?

Answer 14

A more globular protein

Question 15

What is the structure that tertiary proteins may turn into?

Answer 15

Quaternary structures

Question 16

What are the two types of quaternary structures?

Answer 16

Homodimer or Heterodimer complex

Question 17

What is a homodimer? What is a heterodimer complex?

Answer 17

Homodimer = 2 + of the same proteins being put together

Heterodimer complex = 2 + different proteins put together

Question 18

What happens if there is a mistake in the mRNA for the protein? How does this affect the tertiary/quaternary structure?

Answer 18

Substitutes in a different amino acid

This can result in the proteins being folded differently

Question 19

What amino acid is important for creating covalent bonds in the tertiary/quaternary structures? What happens if this amino acid is not present due to incorrect translation?

Answer 19

Cystine - form disulphides bonds

The complex won’t hold therefore it won’t fold over properly

Question 20

What happens to the functionality of the protein if it is not folded properly?

Answer 20

Alters the shape of the binding groove which alters how the target molecules can bind to the binding groove therefore how efficiently it can degrade the molecule

Question 21

Once the polypeptide is released into the cytoplasm, how does it know where to go for further processing/utilisation?

Answer 21

The front end of the polypeptide is a signal peptide

Question 22

What are the two different types of proteins that are processed differently?

Answer 22

Secretory proteins - fully translocated into the ER

Membrane protein - 1+ hydrophobic segments of polypeptide chain anchor it in bilayer

Question 23

Explain how the polypeptide begins the process for folding

Answer 23

1 - first few amino acids are recognised by a translocating protein
2 - the translocating protein takes the polypeptide and takes it into one of the pores on the rough ER
3 - The signal peptide is removed from the polypeptide
4 - the polypeptide chain is inserted into the endoplasmic reticulum lumen to be folded

Question 24

Where is the signal peptide found on the polypeptide?

Answer 24

At the N-terminus

Question 25

What happens to the folded polypeptide chain after processing in the ER?

Answer 25

Goes to the golgi body for further processing then either get secreted, goes into one of the intracellular organelles or onto the membrane

Question 26

What is phosphorylation?

Answer 26

The addition of a phosphate group onto a proteins

Question 27

When is post translational modification done?

Answer 27

Following transcription and translation

Question 28

Post translational modification is heavily controlled for what kind of proteins?

Answer 28

Signal proteins

Question 29

What are some of the post translational modifications that can be done to a protein?

Answer 29

Methylation (addition of a methyl group)
Acetylation (addition of an acetyl group)
Biotinylation (addition of biotin)
Carboxylation (addition for carboxylic acid group)
Carbohydrate addition (addition of carbohydrate, particularly for membrane bound proteins FYI)