Topic 4 - Proteins

Question 1

Definition of electronegativity?

Answer 1

Electronegativity is a measure of the tendency of an atom to attract a bonding pair of electrons.

Question 2

What two factors impact electronegativity?

Answer 2

1. Nuclear charge
2. Shielding

As you go from left to right in the periodic table electronegativity increases –> increase in nuclear charge. Likewise, electronegativity increase down to up due to the decrease in shielding by non-valence electrons (Fewer orbitals between nucleus and valence electrons).

Question 3

Do dipoles in polar bonds line up?

Answer 3

Yes, polar dipoles line up because it is energetically favourable.

Question 4

Describe the energy level diagram for the polar bond?

Answer 4

The more electronegative orbitals are closer in energy to the new hybrid orbital –> this means that the electron spends more time closer to the more electronegative atom.

For example in this case, the oxygen atom holds on the electron more tightly (more favourable).

Question 5

Draw the unequal distribution of electron density in a polar bond (σ and π bonds).

Answer 5

The shape of the orbitals shows us that there is a greater electron density near the more electronegative atom (Electrons spends more time there).

Question 6

Explain the Lennard-Jones Potential?

Answer 6

The Lennard-Jones potential shows us the interaction between two atoms as they come closer and closer.

1. There are favourable V.D.W interactions as the distance between the two atoms decrease (dipole to dipole interactions)
2. Repulsion will occur as well the closer the two molecules are –> atoms repel (electron cloud repulsion) –> coulombs repulsion.

As both curves for repulsion and attraction diverge –> we get a minimum which corresponds to the most optimal distance (shown by the net graph). This distance is known as the optimal van der Waals radii (forces cancel each other out –> equilibrium separation)

Sum of the van der Waals radii is the closest point the molecules can come together.

Question 7

How do you define the distance between two atom centres?

Answer 7

2 x the radii of the atoms

Question 8

When does steric clash occur?

Answer 8

It occurs when atoms are pushed closer than the sum of their Van der Waals radii.

It is extremely unfavourable but if we have a source of energy we can push atoms closer together,.

Question 9

Explain the hydrophobic effect.

Answer 9

Water molecules are in contact with the non-polar surface –> only able to form H-bonds with other water molecules –> not the Non-polar surface.

This forces the water molecules to arrange themselves in a particular orientation –> degrees of freedom decrease –> water forms a clathrate (cage) at the non-polar surface. Results in an increase in order/decrease in entropy. Unfavourable as it doesn’t flow the 2nd law of thermodynamics.

Once both non-polar surfaces are together/hidden there is an increase in free water molecules –> decrease in order/increase in entropy.

Entropy is the driving force.

Question 10

How to draw hydrogen bonds? What are the two key characteristics that one must remember when drawing them?

Answer 10

H-bonds –> permanent dipole –> as soon as the bond is formed –> dipole is present

Note –> dipole arrow always points to the positive charge.

1. H-bonds between two molecules are always linear —-> Hydrogen atom will be between the two nuclei –> Lined up.
2. Hydrogen bond dipoles arrows must align.

Question 11

Are hydrogen bond fixed in place?

Answer 11

Yes, hydrogen bonds in Biochemistry are fixed in place.

Question 12

Place all the hydrogen bonds from most to least polar?

1. N-H and H-O
2. O-H and O=C
3. N-H and O=C
4. O-H and H-O

Answer 12

As you go down the list the H-bonds become weaker/smaller dipoles.

Donor Acceptor

1. O-H and O=C
2. O-H and H-O
3. N-H and O=C
4. N-H and H-O

Question 13

How are Van der Waals interactions formed?

Answer 13

V.D.W forces arise from transient dipoles which result in induced dipoles in surrounding atoms.

Sometimes the electrons spend more time in one region of an atom than another –> results in a centre if negative charge –> this will repel electrons in surrounding atoms –> result in an induced dipole –> dipoles interact and energetically favourable interactions are formed.

This interaction is only for a brief period of time.

Question 14

What is the energy of interaction (V.D.W) inversely proportional to?

Answer 14

The energy of interaction of dipole to dipole is inversely proportional to 1/d⁶ .

Question 15

How do H-Bonds and V.D.W forces differ between chemists and biochemists?

Answer 15

1. Weak interactions in Biochem

Fixed dipoles –> H-bonds

Transient dipoles –> V.D.W interactions

2. Weak Interactions in chemistry
3. Fixed dipoles –> H-bonds
4. London forces

Question 16

Bond energy’s for covalent bonds, H-bonds, V.D.W, hydrophobic effect and rotational conformation?

Answer 16

Bond energy’s

Covalent bond –> ≈ 350 KJ/mol

H-bonds –> ≈ 5-20 KJ/mol

V.D.W —> ≈ 0.2-2 KJ/mol

Hydrophobic effect –> entropy driven

Rotational conformations –> ≈ 10KJ/mol.

Question 17

In biological systems do amino acids have an L or D configuration?

Answer 17

Relative stereochemistry –> L or D

In living systems, amino acids are found in their L configuration. Barely any of the D configurations are present.

Question 18

How to interconvert between L and D amino acid configuration?

Question 19

How is a peptide bond between two amino acids formed?

Answer 19

Condensation reaction which releases water.

Note –> peptide backbone created includes everything except for the R-groups.

Question 20

Definition of a peptide?

Answer 20

Peptide –> when two or more amino acids are linked by a peptide bond.

Question 21

Definition of a polypeptide?

Answer 21

Polypeptide –> ‘Lots’ of amino acids are linked by peptide bonds.

Question 22

What do the N-terminus and C-terminus refer to?

Answer 22

On each peptide/polypeptide, you will have one end containing an NH₂ group which is the N-terminus. While on the other end you have a -COOH group which is the C-terminus.

This gives peptides and polypeptides directionality.

Question 23

What do they call amino acids when found in a peptide/polypeptide?

Answer 23

They are called amino acid residues –> what’s left after the H₂O is lost.

Question 24

Is the backbone of a peptide backbone charged?

Answer 24

No the peptide backbone is NOT charged.

Question 25

What is the primary structure of a polypeptide?

Answer 25

The primary structure of a protein is the level of protein structure which refers to the specific sequence of amino acids which are linked by covalent bonds.

Question 26

What is the simple way to write out an amino acid sequence?

Answer 26

Simply naming the amino acid side chains.

R₁R₂R₃R₄ etc.

Question 27

Explain/draw the resonance structure of a peptide bond?

Answer 27

The electron moves between the Nitrogen and the oxygen which results in the movement of the double bond –> results in resonance.

Question 28

Do dipoles arise when the peptide bond forms a conjugate system?

Answer 28

Question 29

What are the bond distances and angles in the peptide bond?

Answer 29

Question 30

What are the trans and cis configurations of peptide bonds?

Answer 30

The orientation of the rest of the peptide backbone relative to a single peptide bond can either be cis (same) or trans (opposite).

To interconvert one needs roughly 10 KJ/mol –> change in configuration requires you to break a π bond.

Trans configuration is preferred because in the cis configuration the peptide chains are close to each other –> crowded –> steric clash –> results in an energy penalty –> Trans is energetically more favourable.

Question 31

How to interconvert between cis and trans-peptide bonds? How much energy is needed?

Answer 31

You need to break and form Pi bonds.

Energy needed is 10 kJ/mol

Question 32

What are the two different types of abbreviations for amino acids?

Answer 32

2 types of abbreviations

1. 3 letter abbreviation –> i.e. Alanine –> Ala
2. 1 letter abbreviation –> i.e. Alanine –> A

Question 33

What is the structure and the abbreviations of alanine?

Answer 33

Three letter abbreviation: Ala

Single Letter abbreviation: A

Question 34

What is the structure and the abbreviations of Valine?

Answer 34

Three letter abbreviation: Val

Single Letter abbreviation: V

Question 35

What is the structure and the abbreviations of Leucine?

Answer 35

Three letter abbreviation: Leu

Single Letter abbreviation: L

Question 36

What is the structure and the abbreviations of Isoleucine?

Answer 36

Three letter abbreviation: Ile

Single Letter abbreviation: I

Question 37

What is the structure and the abbreviations of Glycine?

Answer 37

Three letter abbreviation: Gly

Single Letter abbreviation: G

Question 38

What is the structure and the abbreviations of Proline?

Answer 38

Three letter abbreviation: Pro

Single Letter abbreviation: P

Question 39

What is the structure and the abbreviations of cysteine?

Answer 39

Three letter abbreviation: Cys

Single Letter abbreviation: C

Question 40

What is the structure and the abbreviations of methionine?

Answer 40

Three letter abbreviation: Met

Single Letter abbreviation: M

Question 41

What is the structure and the abbreviations of histidine?

Answer 41

Three letter abbreviation: His

Single Letter abbreviation: H

Question 42

What is the structure and the abbreviations of phenylalanine?

Answer 42

Three letter abbreviation: Phe

Single Letter abbreviation: F

Question 43

What is the structure and the abbreviations of tyrosine?

Answer 43

Three letter abbreviation: Tyr

Single Letter abbreviation: Y

Question 44

What is the structure and the abbreviations of Tryptophan?

Answer 44

Three letter abbreviation: Trp

Single Letter abbreviation: W

Question 45

What is the structure and the abbreviations of asparagine?

Answer 45

Three letter abbreviation: Asn

Single Letter abbreviation: N

Question 46

What is the structure and the abbreviations of Glutamine?

Answer 46

Three letter abbreviation: Gln

Single Letter abbreviation: Q

Question 47

What is the structure and the abbreviations of Serine?

Answer 47

Three letter abbreviation: Ser

Single Letter abbreviation: S

Question 48

What is the structure and the abbreviations of Threonine?

Answer 48

Three letter abbreviation: Thr

Single Letter abbreviation: T

Question 49

What is the structure and the abbreviations of Lysine?

Answer 49

Three letter abbreviation: Lys

Single Letter abbreviation: K

Question 50

What is the structure and the abbreviations of arginine?

Answer 50

Three letter abbreviation: Arg

Single Letter abbreviation: R

Question 51

What is the structure and the abbreviations of aspartic acid?

Answer 51

Three letter abbreviation: Asp

Single Letter abbreviation: D

Question 52

What is the structure and the abbreviations of glutamic acid?

Answer 52

Three letter abbreviation: Glu

Single Letter abbreviation: E

Question 53

How to name the different carbons in amino acids?

Answer 53

1. Alpha
2. Beta
3. Gamma
4. Delta
5. Epsilon

Question 54

What are the enantiomers and diastereomers of isoleucine?

Answer 54

Question 55

How many different amino acids are there (encoded by the genetic code)?

Answer 55

There are 20 amino acids that are encoded by the genetic code.

Question 56

How many different amino acids can be found in proteins?

Answer 56

More than 100 amino acids found in proteins –> this is because the a.a change when present in proteins due to different interactions.

Question 57

How many and what are the essential amino acids?

Answer 57

There are 9 essential amino acids

They are: His, IIe, Leu, Lys, Met, Phe, Thr, Val, Trp.

Question 58

What are the torsion angles in the peptide backbone?

Answer 58

Torsion angles refer to the single bond rotation of the C-C (Psi - Ψ) and C-N (Phi - Φ) bonds in a peptide bond.

These bonds can rotate which results in different conformations.

They are dihedral angles.

Question 59

Explain the Ramachandran plot?

Answer 59

The Ramachandran plot shows us the different Psi and Phi angles which are allowed/preferred.

Any Psi or Phi angles that are not in the allowed/preferred region are not energetically favourable due to steric clash –> groups are clashing.

As one can see there are at a set of Psi and Phi angles that are needed for the formation of Alpha helices and Beta pleated sheets –> these angles allow for favourable V.D.W interactions.

In Alpha helix:

• Favourable –> V.D.W forces and H-bonds
• A.A packed tightly –> minimal/no gap in helix.

Question 60

Explain the structure of β pleated sheets?

Answer 60

β pleated sheets

Consists of alpha-like helices that are stretched out –>, however, this doesn’t allow the formation of H-bonds within a strand –> hence, multiple strands come together to form H-bonds –> results in barrel formation.

Note –> Strands in β pleated sheets run anti-parallel.

Question 61

Explain the structure of alpha helices.

Answer 61

Alpha helices formed by the coiling up primary structure –> results in the formation of H-bonds between C=O and H-N between non-adjacent amino acids.

Note –> there is no space inside the helix –> side chains face towards the outside.

General facts

1. 1.5 Å rise between amino acid residue
2. 3.6 residues per turn in the helix.
3. 7.2 residues to reach the same place as before.

Question 62

What is the definition of the secondary structure of a protein? What are some key characteristics?

Answer 62

Definition: Arrangement of a polypeptide into a regular alpha helix, beta structure, or random coil configuration by the formation of intramolecular hydrogen bonds.

Characteristics:

1. Ideal peptide bond geometry (planar)
2. Ideal V.D.W interactions –> lowest point of Lenard John’s potential –> favourable (Phi and Psi angles).
3. Ideal H-bond geometry

Question 63

How are multiple coils of alpha helices arranged?

Answer 63

Alpha helices are amphipathic

Multiple helices come together by twisting around each other. The hydrophobic effect between multiple helices keeps them together.

Example: Keratins –> found in skin, hair and nails.

Heptad repeat –> sequence of 7 hydrophobic amino acids typically used to hold together coiled coils.

Question 64

Explain the key characteristics of globular protein structures? (Alpha and beta)

Answer 64

Alpha helices and beta strands can also be found in a globular form –> this occurs when multiple helices/strands are broken up by irregular secondary structures.

Question 65

Explain the structure of fibroin proteins.

Answer 65

Fibroin –> Protein found in silk created by spiders.

1. Multiple B-strands are held together by Hydrogen bonding –> creates sheets. (Side chains –> Zip up nicely)
2. These sheets can then be stacked on top of each other –> held together by V.D.W interactions and some hydrophobic effect.

Question 66

When amino acids are packed in a protein core –> how much space can be occupied (percentage wise)?

Answer 66

Up to 75% can be filled up –> due to the different sized atoms.

Question 67

What amino acid is used to minimise steric clash and to achieve tight turns?

Answer 67

Glycine –> it has conformational flexibility –> this is because it has no side chain at all (only -H) –> minimal steric clash –> allows for more allowed/preferred Psi and Phi angles.

This allows polypeptides to make tight turns –> only takes two a.a to make the sharp turn with glycine.

Question 68

Which amino acids are Aliphatic?

Answer 68

Definition of aliphatic –> organic compound that has a straight chains, branched chains, or non-aromatic rings.

This includes Alanine, Valine, Leucine, Isoleucine.

Question 69

Which amino acids are non-polar?

Answer 69

Non-polar A.A –> Glycine, Proline, cysteine, methionine.

Question 70

Which amino acids are aromatic?

Answer 70

Aromatic A.A –> Histidine, Phenylalanine, Tyrosine, Tryptophan.

Question 71

Which amino acids are polar?

Answer 71

Polar A.A –> Asparagine, Glutamine, Serine, Threonine.

Question 72

Which amino acids are charged?

Answer 72

Charged A.A –> Lysine, Arginine, Aspartic acid, Glutamic acid.

Question 73

What are protein kinases and phosphatases?

Answer 73

Both are enzymes

Protein kinases –> Add Phosphates to amino acids

Protein phosphatases –> cleaves off phosphates from amino acids.

Question 74

Common post-translational modification for Serine?

Answer 74

Question 75

Common post-translational modification for glutamic acid?

Answer 75

Note that both -COOH groups are deprotonated as well –> important so that it can interact with Ca²⁺

This A.A is important for blood clotting.

Question 76

Common post-translational modification for cysteine?

Answer 76

Sulfhydryl groups in Cysteine amino acids undergo oxidation (releases 2 H⁺) to form disulphide bond.

Normally this post-translational modification occurs in the secretory pathway.

Question 77

What is the definition of a denatured protein?

Answer 77

Denaturation is the alteration of a protein shape through some form of external stress ( heat, acid or alkali) –> no longer be able to carry out its cellular function.

Opposite of folded protein –> unfolded.

Question 78

Definition of a random coil?

Answer 78

Random coil refers to a protein that does not have a 3^o structure.

Question 79

What is the change in Gibbs free energy between a random coil and a folded protein?

Answer 79

Random coil <—-(Folding/unfolding)——> Folded

ΔGº = -50 KJ/Mole from random to folded.

Question 80

How to long-range interactions stabilise protein structures?

Answer 80

Long-range interactions lock the whole structure in place and stabilise the protein structure.

Example: The cysteine disulphide bridge locks the structure in place.

Question 81

What determines the secondary and tertiary structures?

Answer 81

The amino acid sequence ultimately determines the 2^o and 3^o structure. A.A sequence determined by genetic code.

Question 82

Explain the structure of collagen.

Answer 82

Collagen

It is composed of 3 strands that twist around each other –> problem –> steric clash/no space.

Solution? –> use glycine as it allows the packing of 3 twisted strands –> Glyc - x - y –> every third amino acid is glycine –> results in another problem –> glycine results in increased flexibility.

Solution? –> Use proline (X or Y) –> decreases flexibility –> forms ring which fixes Phi angle.

Question 83

What is an important characteristic of proline in a protein?

Answer 83

Proline amino acids form a ring structure –> reduces flexibility as keep the Phi angle fixed.

Question 84

What are oligomeric proteins?

(Quaternary structure)

Answer 84

Oligomeric proteins –> refers to the assembly of two or more polypeptides into a protein.

A single polypeptide in a 4^o structure is referred to as a subunit.

Question 85

Nomenclature for oligomeric proteins?

• Number of polypeptide subunits
• Different/identical polypeptide subunits
• Domain

Answer 85

• Number of polypeptide subunits –> dimer, trimer, tetramer, etc
• Different/identical polypeptide subunits –> Homo-, hetero-.
• Domain (different subunits) –> Alpha, Beta, etc.

Example:

Heterotrimer αβγ

Question 86

Definition of a tertiary structure?

Answer 86

Tertiary structure –> When polypeptide folds to form a 3D arrangement (also known as native proteins) –> formed by long-range interactions between amino acids.

Question 87

Why is it useful to have anti-parallel strands in a Beta structure?

Answer 87

Anti-parallel allows for sharp turns.

Question 88

Are aromatic rings in a.a planar?

Answer 88

Yes, they are planar because the atoms are Sp² hybridized.

Question 89

What are the two different ways a heterodimer can arise?

Answer 89

1. Two genes code for the two different subunits –> they join together
2. Single gene codes for both subunits –> Proteases cleaves them –> join together via different attractions.

Question 90

Are amino acids chiral?

Answer 90

With four different groups connected to the tetrahedral alpha-carbon atom, alpha-amino acids are chiral: they may exist in one or the other of two mirror-image forms, called the L isomer and the D isomer.

Important to note that only L isomers are found in proteins.

Question 91

How does the ionization state of amino acids change with pH?

Answer 91

Amino acids in solution at neutral pH exist predominantly as dipolar ions (also called zwitterions). In the dipolar form, the amino group is protonated (NH₃⁺) and the carboxyl group is deprotonated (COO^-).

In acid solution (e.g. pH 1), the amino group is protonated (-NH₃⁺) and the carboxyl group is not dissociated (-COOH).

As the pH is raised, the carboxylic acid is the first group to give up a proton, inasmuch as its pKa is near 2. The dipolar form persists until the pH approaches 9, when the protonated amino group loses a proton.

Question 92

Is imidazole ring in histidine uncharged or positively charged in biological systems?

Answer 92

Histidine contains an imidazole group, an aromatic ring that also can be positively charged (Figure 2.9). With a pKa value near 6, the imidazole group can be uncharged or positively charged near neutral pH, depending on its local environment.

Question 93

Typical pka values for the ionization for Terminal Carboxyl, aspartic acid, glutamic acid, histidine, terminal amino group, cysteine, tyrosine, lysine and arginine.

Answer 93

Question 94

Does a polypeptide chain have directionality?

Answer 94

A polypeptide chain has directionality because its ends are different: an alpha-amino group is present at one end and an alpha-carboxyl group at the other.

Note –> sequence of amino acids in a polypeptide chain is written starting with the amino-terminal residue.

Question 95

What is 1 Dalton equal to?

Answer 95

1 Dalton is equal to one atomic mass unit (1 g mol^-1)

A protein with a molecular weight of 50,000 g mol^-1 has a mass of 50,000 daltons, or 50 kDa (kilodaltons).

Question 96

Does the polypeptide backbone have a high hydrogen bonding potential?

Answer 96

The polypeptide backbone is rich in hydrogen- bonding potential. Each residue contains a carbonyl group (C=O), which is a good hydrogen-bond acceptor, and, with the exception of proline, an NH group, which is a good hydrogen-bond donor.

Question 97

What is the geometry of the protein backbone?

Answer 97

The protein backbone follows a planar geometry –> due to the resonance structure of the peptide bond –> results in Sp² hybridisation –> results in a planar molecule.

This partial double bond character is evident from bond lengths –> between the values of a single and double bond –> 1.32 A.

Question 98

What are the two configurations for a planar peptide bond?

Answer 98

In the trans configuration, the two a-carbon atoms are on opposite sides of the peptide bond. In the cis configuration, these groups are on the same side of the peptide bond.

Almost all peptide bonds in proteins are trans –> due to steric hindrance –> less clashing of groups

Question 99

What bonds in amino acid residues are able to rotate?

Answer 99

Bonds between the amino group and the a-carbon atom and between the a-carbon atom and the carbonyl group are pure single bonds.

This freedom of rotation about two bonds of each amino acid allows proteins to fold in many different ways.

Question 100

How are the secondary structures formed?

Answer 100

Alpha helices, B-strands, and turns are formed by a regular pattern of hydrogen bonds between the peptide N-H and C=O groups of amino acids that are near one another in the linear sequence.

Question 101

Explain the structure of an alpha helix?

Answer 101

Alpha-helix –> is a rodlike structure –> tightly coiled backbone forms the inner part of the rod and the side chains extend outward in a helical array.

Stabilized by hydrogen bonds between the NH and CO groups of the main chain. In particular, the CO group of each amino acid forms a hydrogen bond with the NH group of the amino acid that is situated four residues ahead in the sequence.

Hence, except for amino acids near the ends of an alpha-helix, all the main-chain CO and NH groups are hydrogen bonded.

Question 102

Description of the alpha-helical structure (number wise).

Answer 102

Each residue is related to the next one by a rise, also called translation, of 1.5 Å along the helix axis and a rotation of 100 degrees, which gives 3.6 amino acid residues per turn of the helix.

Hence –> amino acids spaced three and four apart in the sequence are spatially quite close to one another in an alpha-helix whereas, amino acids that are spaced two apart are on opposite sides of the helix.

The pitch of the alpha-helix is the length of one complete turn along the helix axis and is equal to the product of the rise (1.5 Å) and the number of residues per turn (3.6), or 5.4 Å.

Question 103

What is the ‘screw’ of an alpha-helix?

Answer 103

The screw sense –> alpha helix can be right-handed (clockwise) or left-handed (counter-clockwise)

Both conformations are allowed but…

right-handed helices are energetically more favourable because there is less steric clash between the side chains and the backbone.

Question 104

Which amino acids are not suitable for an alpha-helix?

Answer 104

1. Branching at the beta-carbon atom, as in valine, threonine, and isoleucine, tends to destabilize alpha-helices because of steric clashes.
2. Serine, aspartate, and asparagine also tend to disrupt alpha-helices because their side chains contain hydrogen-bond donors or acceptors in close proximity to the main chain, where they compete for main-chain NH and CO groups.
3. Proline also is a helix breaker because it lacks an NH group and because its ring structure prevents it from assuming the Phi value to fit into an alpha-helix

Question 105

Describe the structure of Beta strands.

Answer 105

Beta pleated sheets –> 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.

The distance between adjacent amino acids along the same beta strand is approximately 3.5 Å, in contrast with a distance of 1.5 Å along an alpha helix. The side chains of adjacent amino acids point in opposite directions.

Question 106

Explain the structure of Beta-pleated sheets.

Answer 106

A beta-sheet is formed by linking two or more beta strands lying next to one another through hydrogen bonds. Adjacent strands in a beta sheet can run in opposite directions (antiparallel b-sheet) or in the same direction (parallel b-sheet).

Antiparallel

The NH group and the CO group of each amino acid are respectively hydrogen bonded to the CO group and the NH group of a partner on the adjacent chain

Parallel

Hydrogen-bonding scheme is slightly more complicated.

NH group is hydrogen bonded to the CO group of one amino acid on the adjacent strand, whereas the CO group is hydrogen bonded to the NH group on the amino acid two residues farther along the chain.

Note –> Many strands, typically 4 or 5 but as many as 10 or more, can come together in Beta sheets. Such Beta sheets can be purely antiparallel, purely parallel, or mixed.

Question 107

How are Beta-sheets schematically represented?

Answer 107

In schematic representations, beta-strands are usually depicted by broad arrows pointing in the direction of the carboxyl-terminal end to indicate the type of b-sheet formed—parallel or antiparallel. More structurally diverse than alpha-helices, b-sheets can be almost flat but most adopt a somewhat twisted shape.

Question 108

How are proteins able to make compact globular structures?

Answer 108

Most proteins have compact, globular shapes owing to reversals in the direction of their polypeptide chains. Many of these reversals are accomplished by a common structural element called the reverse turn.

In many reverse turns, the CO group of residue i of a polypeptide is hydrogen bonded to the NH group of residue i + 3. This interaction stabilizes abrupt changes in direction of the polypeptide chain.

Other cases, more-elaborate structures are responsible for chain reversals. These structures are called loops or sometimes Ω loops –> loops do not have regular, periodic structures but they are rigid and well defined.

Question 109

What are the structures of the helices in alpha-keratin?

Answer 109

Alpha-keratin –> two right-handed alpha helices intertwined to form a type of left-handed superhelix called an alpha-helical coiled coil –> part of the coiled-coil protein family –> consists of two or more alpha helices that entwine to form a stable structure.

Two helices in alpha-keratin associate with each other by weak interactions such as van der Waals forces and ionic interactions.

Members of this family are characterized by a central region of 300 amino acids that contains imperfect repeats of a sequence of seven amino acids called a heptad repeat.

Question 110

Explain the structure of the collagen protein.

Answer 110

• This extracellular protein is a rod-shaped molecule, about 3000 Å long and only 15 Å in diameter. It contains three helical polypeptide chains, each nearly 1000 residues long.
• Glycine appears at every third residue in the amino acid sequence, and the sequence glycine-proline-hydroxyproline (like proline but has -OH group attached to proline ring) recurs frequently.
• Hydrogen bonds within the strand are absent –> instead the helix is stabilized by steric repulsion of the pyrrolidine rings of the proline and hydroxyproline residues
• Strands wind around one another to form a superhelical cable that is stabilized by hydrogen bonds between strands –> H-bonds between the peptide NH groups of glycine residues and the CO groups of residues on the other chains + hydroxyl groups of hydroxyproline residues also participate in hydrogen bonding.

Question 111

Why is glycine required in the collagen polypeptides?

Answer 111

The inside of the triple-stranded helical cable is very crowded and accounts for the requirement that glycine is present at every third position on each strand –> not bulky (no side chain) –> so its the only residue that can fit in an interior position.

The amino acid residue on either side of glycine is located on the outside of the cable, where there is room for the bulky rings of proline and hydroxyproline residues

Question 112

What are motifs/super-secondary structures?

Answer 112

Motifs/super-secondary structures –> Certain combinations of secondary structure are present in many proteins and frequently exhibit similar functions.

For example, an alpha-helix separated from another alpha helix by a turn called a helix-turn-helix unit is found in many proteins that bind DNA

Question 113

Definition of domain?

Answer 113

Some polypeptide chains fold into two or more compact regions that may be connected by a flexible segment of the polypeptide chain. These compact globular units, called domains.

Question 114

In the quaternary structure, what do you call different polypeptides?

Answer 114

Subunits.

Question 115

What determines the 3D structure of a protein?

Answer 115

The amino acid sequence –> primary structure.