Lecture 2

Question 1

Oligopeptide

Answer 1

< 40 AAs

Question 2

Polypeptide

Answer 2

MW < 10,000 Da

Question 3

Protein

Answer 3

MW > 10,000 Da

Question 4

Where can rotation occur in proteins? What are these angles called and what are they influenced by?

Answer 4

Between the alpha carbon and Nitrogen and between alpha carbon and carbon

Phi and psi, influenced by steric interactions of R groups

Question 5

What gives rise to secondary structure?

Answer 5

Polar characteristic of the peptide bond: The fact that peptide bonds form hydrogen bonds between residues in the same polypeptide.

Question 6

What does hydrogen bonding between peptide groups in residues result in?

Answer 6

Minimized steric strain

Position side groups to minimize interference

leads to formation of either alpha helix or beta pleated sheet because those secondary structures meet these qualifications

Question 7

What is the length of 1 turn of alpha helix in angstroms? In residues?

Answer 7

5. 4 A

3. 6 residues

Question 8

Where do r groups reside in helix? What interactions occur in the core?

Answer 8

R groups are projected out into environment to interact with aqueous environment

Center is peptide backbone, atoms in center are in contact via Van der Waals forces

Question 9

Which 2 residues are least likely to be found in an alpha helix? Why?

Answer 9

Proline: fact that amino nitrogen is incorporated in side group introduces a destabilizing kink into helix when present

Glycine: too much conformational flexibility due to small size

Question 10

What other 2 factors affect stability alpha helix?

Answer 10

Presence of similar charged residues next to one another that produces repulsive forces

Presence of bulky side groups producing steric hindrance

Question 11

Where are hydrogen bonds in beta pleated sheets?

Answer 11

Between adjacent strands.

Question 12

What amino acids are more commonly found in beta pleated sheets and why?

Answer 12

Small amino acids (glycine and alanine)

Question 13

Beta turns link ____ sheets

Beta loops link _____ sheets

Answer 13

Antiparallel

Parallel

Question 15

Define tertiary structure.

Answer 15

The 3D shape of a protein including regular and irregular secondary structure and spatial arrangement of side groups

Question 16

What 2 amino acids are commonly found in beta turns and beta loops?

Answer 16

Proline and glycine

Question 17

Define tertiary structure.

Answer 17

3D shape of protein including regular and irregular secondary structures and spatial arrangement of side chains

Question 18

Describe the hydrophobic core of globular proteins.

Answer 18

The core contains hydrophobic amino acids. But it can also contain residues that are individually polar or charged as long as those residues associate with one another to yield a net neutral charge. These polar or charged species are usually present in the core for structural purposes to help stabilize the native conformation.

Question 19

What is a motif?

Answer 19

A spatial arrangement involving 2 or more elements of secondary structure.

Question 20

Describe a domain.

Answer 20

Refers to tertiary structure. A domain is a part of the protein that is independently stable and often possess its own structure and function separate from the rest of the protein.

Question 21

What is the major driving force behind protein folding? Why?

Answer 21

The aggregation / collapse of non polar groups into a molten globule state in aqueous solution is the major force driving protein folding. This aggregation displaces water molecules surrounding the protein, which increases entropy and offsets the loss of entropy from the increased order of the protein itself. This is driven because it ultimately results in an increase in entropy of the universe and produces a conformation that is at the lowest Gibbs free energy and thus the most stable.

Question 22

What other factors stabilize protein structure (less significant stabilization than hydrophobic effect)? (4)

Answer 22

Van der Waals forces
Hydrogen bonding
Ionic interactions
Disulfide bonds

Question 23

Why do hydrogen bonds and ionic interactions not contribute as substantially to the stabilization of the protein?

Answer 23

Because they are polar / charged and able to interact with water in the environment, which detracts from their ability to interact with each other and fold / stabilize the protein.

Question 24

If polar or charged groups are found in the core of the protein, what must be true of those groups?

Answer 24

In the core of the protein there is no water present and there is a large amount of hydrophobic residues. Thus, in order for polar and charged groups to be found in the core of the protein, the groups must have a stabilizing effect on the structure of the protein and they must associate with one another such that they are neutral in charge / dipole interactions.

Question 25

What did the Anfinsen experiment discover?

Answer 25

In the Anfinsen experiment, a sample of active ribonuclease A was exposed to urea (to disrupt non covalent bonds) and beta mercaptoethanol (to break di sulfide bonds). The sample was tested for activity and found to be inactive under these disruptive conditions. The urea and BME were then removed and the activity was measured again and the protein was found to have similar activity as it did prior to urea and BME. This led Anfinsen to conclude that the primary sequence has all the necessary information needed for proteins to fold into native conformation.

Question 26

What are the 2 events in protein folding?

Answer 26

First, local segments fold into secondary structures. Second, the whole protein undergoes hydrophobic collapse into molten globule.

Question 27

What is a molten globule?

Answer 27

Formation of a molten globule describes the spontaneous collapse of the polypeptide into a compact state (the molten globule). This is driven by the hydrophobic effect and there are many intermediate states that occur between the initial state and the native conformation. As the protein folds more at each of these intermediate states, the number if possible confirmations is reduced until only 1 state with the lowest possible energy is possible and that is the native conformation.

Question 28

What do chaperones do?

Answer 28

Chaperones are proteins that assist in folding of a polypeptide. They don’t physically fold the protein, but they provide an environment that aids the protein in folding to the lowest possible energy state. As there are many possible folding states with different energies, chaperones help proteins overcome these barriers and fold the the native state and not get stuck as a misfolded protein.

Question 29

How does protein misfolding relate to Alzheimer’s?

Answer 29

Newly synthesized amyloid protein can misfold. That misfolded protein can be degraded, but in the disease state it can also aggregate with other misfolded proteins. Continued aggregation of misfolded proteins leads to clumps of protein that are non functional and are so large that they can no longer be degraded effectively. These clumps clog up the cells machinery causing the symptoms of Alzheimer’s.

Question 30

What is the general structure of collagen?

Answer 30

Three left handed helices that come together to form a right handed helix overall