Chapter 4 - Protein 2, 3, 4 structure

Question 1

Secondary structures are stabilized by ______ b/w nearby amino acids in ________ structure. They contribute to regular arrangements like…(5) Which arrangements are 50% globular protein?

Answer 1

H-bonds; primary
α-helix, β-sheet, Beta Bends， nonrepetitive secondary structure, super-secondary structures & motifs
α-helix, β-sheet, Beta Bends

Question 2

A-helix is the most ________ polypeptide helix. It is a rigid, ______________ structure, tightly packed, coiled polypeptide backbone core.
H-bonds: stabilization of α-helix - each ________ closes a loop containing ___ atoms (ideal).
___ AAs per turn which allows for H-bonding between _____ of 1 AA & __ of AA 3-4 apart in primary sequence.

Answer 2

common; right-handed spiral; n+4 H-bond; 13; 3.6; C=O; NH

Question 3

For a-helix, AA side chain R determines the ability to maintain ______________.

Answer 3

helical structure

Question 4

β strands (almost fully extended): each __ accounts for ~ __-__ nm of the length, _ or more β strands arranged side-by side form β sheets, aligned ______ & stabilized by __ bonds

Answer 4

AA; 0.32-0.34; 2; laterally; H

Question 5

What is intrachain bonding:?

Answer 5

within same polypeptide chain

Question 6

What is interchain bonding?

Answer 6

different polypeptide chains

Question 7

Describe a typical alpha helix structure.

Answer 7

It forms a rigid, right-handed spiral, with a tightly packed polypeptide backbone. The side chains of the AAs extend outward, preventing steric hindrance, and H bonds stabilize the structure. H bonds occur b/w the carbonyl group of one AA and the amide group of an AA that is 3 to 4 residues ahead, forming a characteristic n+4 H-bond pattern.

Question 8

What are the common α helix AA ɸ and ψ angles?

Answer 8

Pitch: 0.54 nm per turn
Rise: 0.15 nm per amino acid
Residues per turn: Around 3.6 amino acids
Torsion angles (ϕ and ψ): Ideal torsion angles are ϕ = -57° and ψ = -47°

Question 9

What are the AAs that disrupt an a-helix structure in polypeptides/proteins?

Answer 9

The AAs are proline and glycine. Proline introduces a kink due to its cyclic structure, preventing rotation around the N-Cα bond. This disrupts the regular H bonding pattern and geometry of the α-helix. For glycine, it is highly flexible due to its small side chain, which allows for too much rotation, making the helical structure less stable.

Question 10

Describe β-pleated sheets.

Answer 10

The alignment of β-strands side by side, forming a sheet-like arrangement. They’re stabilized by H bonds b/w the carbonyl oxygen of one AA and the amide H of another. Unlike α-helices, the H bonds occur b/w different strands rather than w/in a single strand. Each AA contributes ~0.32-0.34 nm to the length of the strand, resulting in an almost fully extended configuration. The pleating of the sheet is in zigzag arrangement of the peptide backbone, where α-carbons are slightly above and below the plane of the sheet.

Question 11

Describe the parallel structure for B-pleated sheets.

Answer 11

Adjacent β-strands run in the same direction (N- to C-terminus). The H bonds between strands are slightly angled, which makes them less stable compared to antiparallel sheets.

Question 12

Describe the antiparallel structure for B-pleated sheets.

Answer 12

Adjacent β-strands run in opposite directions (one strand runs N- to C-terminus while the adjacent strand runs C- to N-terminus). The H bonds in antiparallel sheets are nearly perpendicular to the strands, making them more stable. Each residue forms hydrogen bonds with a single residue on the opposite strand.

Question 13

What are beta bends? Contribute to what?

Answer 13

A type of secondary structure in proteins that create sharp turns in the polypeptide chain. The turns help to reverse the direction of the polypeptide backbone, facilitating the compact and globular shape typical of many proteins. They contribute to the overall tertiary structure of proteins by enabling tight folding and compactness, which is important for protein function and stability.

Question 14

Describe the formation/structure of beta bends.

Answer 14

It usually involves 4 AAs, forming a tight 180˚ turn in the polypeptide chain. The 1st and 4th AAs are often involved in an H bond, stabilizes the turn. The H bond between the carbonyl oxygen of the first AA and the amide hydrogen of the 4th AA. This bond helps stabilize the structure of the bend.

Question 15

What is protein denaturation? What does it primarily affect?

Answer 15

It is the process where a protein loses its native conformation, resulting in the loss of its biological activity. Primarily affects the protein’s secondary, tertiary, and sometimes quaternary structures without breaking its primary sequence of AAs.

Question 16

When does protein denaturation occur?

Answer 16

When external factors like environmental changes or chemical treatments disrupt the non-covalent interactions that stabilize the protein’s structure.

Question 17

What is protein renature? Give an example.

Answer 17

It is the process where a denatured protein refolds back into its native conformation when the denaturing conditions are removed. Not always possible for larger or more complex proteins. For smaller proteins like ribonuclease A, renaturation can occur spontaneously, driven by the free energy change that favors the stable, native conformation.

Question 18

List some factors that could denature a protein.

Answer 18

Heat, pH changes, reducing agents, chaotropic agents, detergents, heavy metal ions and organic solvents.

Question 19

What AA forms “kink” in B-strand structure in polypeptides/proteins?

Answer 19

Proline: Due to its unique cyclic structure, it imposes rigid constraints on the polypeptide backbone, leading to a sharp bend or kink in the strand.

Question 20

How does proline form “kinks” in B-strand structures?

Answer 20

The nitrogen in the peptide bond of proline lacking an H atom, preventing it from participating in the typical H bonding required for regular secondary structures like β-sheets. So, proline disrupts the smooth continuation of the β-strand and creates a structural kink.

Question 21

Give an example of a protein motif with an a-helix.

Answer 21

α-Helix – Loop – α-Helix: commonly found in proteins where 2 α-helices are connected by a loop. The loop allows flexibility and often positions the helices in a way that facilitates protein-protein or protein-DNA interactions.

Question 22

Give an example of a protein motif with an B-sheet.

Answer 22

β-Sheet – Random Coil – α-Helix: a β-sheet is followed by a random coil region and then an α-helix. The random coil region provides flexibility between the structured elements, allowing the protein to fold and function in diverse ways.

Question 23

Give an example of a structural motif.

Answer 23

Beta Bends (Reverse Turns): Not a classic motif, but are structural motifs that link successive strands of antiparallel β-sheets. These turns typically involve 4 amino acids and are stabilized by H bonds.

Question 24

What is a domain?

Answer 24

They are distinct regions of a protein that can fold independently into a stable, 3D structure that typically consists of a combination of α-helices, β-sheets, and loops. Allow proteins to interact with other molecules or perform their catalytic functions.

Question 25

Describe the primary structure of proteins.

Answer 25

The linear sequence of AAs in a polypeptide chain, linked by peptide bonds between the carboxyl group of one AA and the amino group of another. The peptide bonds are covalent and planar, providing a stable backbone for the protein.

Question 26

Describe the secondary structure of proteins.

Answer 26

The regular, repeating local structures formed by the backbone of the polypeptide chain. The most common structures are the α-helix and β-pleated sheet. They are stabilized by H bonds between the carbonyl oxygen and amide hydrogen atoms of the peptide backbone.

Question 27

Describe the tertiary structure of proteins.

Answer 27

Refers to the overall 3D folding of a single polypeptide chain, which is driven by interactions between side chains of the amino acids. Stabilized by disulfide bonds, hydrophobic interactions, H bonds, ionic interactions and Van der Waals interactions.

Question 28

Describe disulfide bonds.

Answer 28

Covalent bonds between the sulfhydryl groups of two cysteine residues, forming a cystine residue.

Question 29

Describe hydrophobic interactions.

Answer 29

Non-polar side chains that tend to cluster together in the interior of the protein, away from water, minimizing contact with the aqueous environment.

Question 30

Where do H bonds occur?

Answer 30

B/w polar side chains or between side chains and backbone atoms.

Question 31

Where do ionic interactions occur?

Answer 31

B/w charged side chains.

Question 32

Where do Van der Waals interactions occur?

Answer 32

Between all atoms in proximity.

Question 33

What proteins facilitate protein folding? How?

Answer 33

Specialized proteins known as chaperones or heat-shock proteins (HSPs). They bind to partially folded or unfolded polypeptides, preventing improper interactions and aggregation during the folding process. They utilize ATP hydrolysis to help proteins fold efficiently and correctly.

Question 34

Give examples of 2 chaperon proteins.

Answer 34

Hsp70 bind to hydrophobic regions of newly synthesized polypeptides to prevent premature folding.
Hsp60 forms a cage-like structure, providing an isolated environment where the polypeptide can fold properly without interference.

Question 35

Give 2 reasons that can cause protein misfolding. Factors? (3)

Answer 35

Mutations in AA sequence (change in primary structure of a protein due to mutations) can prevent the correct folding. Even a single AA substitution can disrupt the normal folding process.
Errors in the folding process (complex and highly regulated process of protein folding can sometimes go wrong), leading to improper folding. Factors like cellular stress, environmental conditions, or deficiencies in molecular chaperones may contribute to errors during folding.

Question 36

Give an example for mutation in AA sequence and errors in the folding process.

Answer 36

Sickle-cell disease is the substitution of one amino acid in hemoglobin.
Alzheimer’s Disease is caused by protein misfolding when the aggregation of amyloid-beta proteins, which form plaques in the brain, leading to neurodegeneration.

Question 37

What are the fates of misfolded proteins?

Answer 37

Targeted for degradation, corrected by chaperones and protein aggregation.

Question 38

What happens when proteins are targeted for degradation?

Answer 38

Misfolded proteins are identified by cellular mechanisms and are marked for degradation by the proteasome, which breaks down the misfolded proteins into smaller peptides.

Question 39

What happens when proteins are corrected by chaperones?

Answer 39

Chaperones bind to misfolded proteins and attempt to refold them into their correct conformation.

Question 40

What happens when proteins are aggregated?

Answer 40

These protein aggregates can accumulate within the cell, causing toxicity and interfering with normal cellular functions.

Question 41

What are fibrous proteins?

Answer 41

A class of proteins characterized by their elongated, rigid, and insoluble structure. Unlike globular proteins, which are compact and soluble, fibrous proteins primarily serve structural and supportive roles in various tissues. Some key characteristics include an elongated shape, repetitive secondary structure, and structural function.

Question 42

What are the major types of fibrous proteins?

Answer 42

Collagen (more than 25% of total protein mass in human body), keratin (in hair, nails and outer layer of skin), and myosin (crucial role in muscle contraction).

Question 43

What is the function of fibrous proteins? Give examples.

Answer 43

Tensile strength and flexibility of various tissues. The intertwining meshwork of collagen and keratin gives skin its strength, while collagen fibers provide support to bones and teeth. The other function is the support and protection.

Question 44

Give 2 examples of globular proteins.

Answer 44

Myoglobin is a globular hemeprotein responsible for storing and facilitating the diffusion of oxygen in muscle tissue.
Hemoglobin is a globular hemeprotein that plays a crucial role in transporting oxygen from the lungs to tissues throughout the body. Consists of 4 polypeptide subunits (2 α and 2 β subunits), each containing a heme group, allowing it to bind and transport oxygen efficiently.