Lecture #06 Common Peptide Structures

Question 1

What Stabilizes Secondary Structure?

Answer 1

• A secondary structure is stabilized exclusively by hydrogen bonding along the backbone.

Question 2

Alpha Helix

Answer 2

○ One of the first proposed secondary structures.

○ The side chains of the amino acids composing the structure extend outward in a helical array.

Question 3

Alpha Helix: Stabilization

Answer 3

○ Stabilized by hydrogen bonds between the NH and CO groups of the main chain. The CO group of each amino acid forms a hydrogen bond with the NH group of the amino acid 4 amino acids away.
§ Thus, all the main-chain CO and NH groups are hydrogen bonded, except for amino acids near the ends of an alpha helix.

Question 4

Alpha Helix Constraints: Steric Effect

Answer 4

○ There are certain amino acids that will not appear in a numerous fashion in an alpha helix structure for constraint reasons.

Steric reasons: valine, isoleucine, threonine. Their side chains would interfere when you try to fold the protein which would create a steric effect.

Question 5

Alpha Helix Constraints: Reactivity

Answer 5

○ There are certain amino acids that will not appear in a numerous fashion in an alpha helix structure for constraint reasons.

§ Reactivity: serine, aspartic acid, and asparagine are H bond donors or acceptors that compete in making hydrogen bonds with main chain CO and NH groups. That is not the desired effect so there is not too many of them.

Question 6

Alpha Helix Constraints: Proline

Answer 6

○ There are certain amino acids that will not appear in a numerous fashion in an alpha helix structure for constraint reasons.

§ Proline will never be found in the interior sequence of a helix. Can be on either or very near the end. This is because its amino group is a cylinder structure, so if you try to make a helix out of a sequence that has proline in it, then the helix would have a bend in it to destabilize it. Often called a helix breaker. Lacks an NH group and its ring structure prevents it from assuming the phi vale to fit into an alpha helix.
□ It’s good to have on the end in case you want to change the folding pattern.

Question 7

Alpha Helix: Arrangement

Answer 7

○ Has a placement of side groups where large ones will not be close to each other but small ones will be close to large ones instead. Create less steric hindrance.

Question 8

Beta-Sheet

Answer 8

○ More extended than alpha helix, which is more compact.
○ R groups and above and below the sheet, to accommodate bulky R groups. So not limited to steric effect as much.
○ Beta sheet means two strands.

Question 9

Beta-Sheet Composition

Answer 9

○ A beta sheet is composed of two or more polypeptide chains called beta strands. A beta strand is almost fully extended rather than being tightly coiled as in the alpha helix.

Question 10

Beta-Sheet Formation

Answer 10

○ A beta sheet is formed by linking two or more beta strands lying next to one another through hydrogen bonds. Adjacent chains can run in opposite (anti-parallel) or in the same (parallel) direction. Opposite end refers to amino and carboxyl being on different sides in each strand, while the opposite occurs in parallel.
§ Geometry of hydrogen bond as a result is a little different between both. Hydrogen bonding forms a square like shape in antiparallel, while it’s skewed to a trapezoid in parallel.

Question 11

Alpha Helix vs. Beta Sheet

Answer 11

• Both helix and sheet are stabilized by hydrogen bonding. Sequence will determine which of the two occurs, and whether the side chains will cause steric effect or not in a helix versus a sheet. Will try to adopt most stable and lowest energy conformation possible with the sequence.
• Most proteins are combinations of the two secondary structures.

Question 12

Protein Interaction With Water

Answer 12

• Proteins are most likely going to be in a water environment, so if they’re not hydrogen bonded with each other, they will be water.

Question 13

Beta Turn

Answer 13

• Third type of secondary structure is beta turn. It is NOT repetitive, relatively short sequence, and can have hydrogen bonds but it won’t be extensive because of short sequence.
○ This structure is important for when you want to change direction in a protein. In a primarily beta sheet structure for example, beta turns can connect the beta sheets together.
○ No defined structure cause of shortness.
○ Important on surface, changing directions, and can interact with water.

Question 14

Tertiary Structure

Answer 14

• Tertiary structure refers to the spatial arrangement of amino acid residues that are far apart in the sequence and to the pattern of disulfide bonds. This level of structure results from interactions of R groups of peptide chain.
• Tertiary structure involves noncovalent interactions between amino acid R groups and the pattern of disulfide bonds. It is what stabilizes them.

Question 15

Folding Proteins Produces…

Answer 15

• Folding of protein develops these “nooks and crannies” in the structure where molecules can bind. Like with an enzyme, a substrate can bind.

Question 16

Disulfide Bond Function

Answer 16

• Disulfide bonds bring far amino acids closer together in folding to stabilize protein.

Question 17

Myoglobin Structure

Answer 17

• Myoglobin has an arrangement of amino acids where charged residues are on the outside and noncharged residues are in the inside, due to the hydrophobic effect. The polypeptide chain therefore folds so that its hydrophobic side chains are buried and its polar, charged chains are on the surface.

Question 18

Domains

Answer 18

• Tertiary structures have independent regions that are connected in a single polypeptide chain, domains. They tell you a little about the function, characteristics, orientation of protein in biological system.

Question 19

Secondary vs. Tertiary

Answer 19

• Secondary structure = hydrogen bonds. Tertiary structure = all the noncovalent interactions plus disulfide bonds.

Question 20

Quaternary Structure

Answer 20

• Quaternary structure is when you combine two or more individual polypeptide chains. They assemble together through noncovalent interactions and sometimes disulfide bonds.

Question 21

Hemoglobin Bonds

Answer 21

• Hemoglobin has absolutely NO dilsuilfide bonds. Tells you that this complex of FOUR individual polypeptide chains is held together by noncovalent interactions.

Question 22

• How can you tell if a protein has tertiary or quaternary structure?

Answer 22

○ Each polypeptide has amino and carboxy terminus. So a protein that’s quaternary, you should have more than one of each. In tertiary, only one of each.

Question 23

Denaturation

Answer 23

• Denaturation means protein is completely unfolded. Lost tertiary and quaternary structure.

Question 24

Causes of Denaturation

Answer 24

• Heat can denature a protein. So can pH.

Question 25

Misfolding

Answer 25

• Misfolding means you may have not lost structure, but have the wrong structure. Possible for protein to be misfolded in a specific region like a domain. Only part of a protein has to be misfolded to affect structure tremendously.

Question 26

Misfolding Produces Aggregate?

Answer 26

• Does a misfolded protein aggregate? Yes it does. When you denature protein, they’re going to expose the hydrophobic residues to water. This causes them to stick together and form an aggregate.