S4-5) Protein Structure

Question 1

Describe the molecular structure of an amino acid

Answer 1

Each amino acid (except for proline) has the following bonded to the α-carbon atom:

• A carboxyl group
• A primary amino group
• A distinctive side chain (“R-group”)

Question 2

How are amino acids be classified?

Answer 2

• Amino acids are classified according to the properties of their side chains
• The nature of the side chains dictates the role an amino acid plays in a protein

Question 3

How do amino acids bond together?

Answer 3

Peptide bonds are formed to link two amino acids together accompanied by the abstraction of a molecule of water (condensation reaction/dehydration synthesis)

Question 4

Describe the 4 unique features of peptide bonds

Answer 4

• Peptide bonds are planar
• Peptide bonds are rigid
• Peptide bonds exhibit a trans conformation
• Bonds on either side of the peptide bond are free to rotate

Question 5

How might amino acids be classified?

Answer 5

• Polar: uneven distribution of electrons
• Nonpolar: even distribution of electrons

Question 6

Describe the structure and formation of a disulphide bond

Answer 6

• The side chain of cysteine contains a sulfhydryl group (–SH)
• In proteins, the –SH groups of two cysteines can become oxidized to form a dimer, cystine, which contains a covalent cross-link called a disulphide bond (–S–S–)

Question 7

What is the significance of disulphide bonds?

Answer 7

• Important component in the active site of many enzymes
• Many extracellular proteins are stabilized by disulphide bonds e.g. Albumin

Question 8

How can one characterise basic and acidic amino acids respectively?

Answer 8

• Acidic amino acids: negatively charged at physiological pH
• Basic amino acids: positively charged at physiological pH

Question 9

What is the value of physiological pH?

Answer 9

pH = 7.35 - 7.45

Question 10

Identify the 2 amino acids with acidic side chains

Answer 10

• Aspartate
• Glutamate

Question 11

Outline the behaviour of amino acids with acidic side chains

Answer 11

• The aspartic and glutamic acid are proton donors
• At physiological pH, the side chains of these amino acids are fully ionized, containing a negatively charged carboxylate group (–COO-)

Question 12

Outline the behaviour of amino acids with basic side chains

Answer 12

• The side chains of the basic amino acids accept protons
• At physiological pH the side chains of strongly basic amino acids are fully ionized and positively charged
• At physiological pH, the side chains of weakly basic amino acids the free amino acid is largely uncharged

Question 13

Identify the 3 amino acids with basic side chains

Answer 13

• Arginine (strongly basic)
• Lysine (strongly basic)
• Histidine (weakly basic)

Question 14

What is the Henderson-Hasselbalch equation?

Answer 14

Question 15

What is the significance of the Henderson-Hasselbalch equation?

Answer 15

The Henderson-Hasselbalch equation expresses the quantitative relationship between the pH of a solution and the [weak acid] and the [conjugate base]

Question 16

What encodes for the amino acid sequence of a protein?

Answer 16

The nucleotide sequence of a gene determines the amino acid sequence of a protein

Question 17

What is determined by the amino acid sequence of a protein?

Answer 17

• The way the polypeptide chain folds
• The physical characteristics of the protein

Question 18

Proteins are polypeptides.

What are polypeptides?

Answer 18

• Polypeptides are macromolecules composed of amino acids
• Amino acids join covalently through peptide bonds to form the sequence of the protein

Question 19

Identify two contrasting factors which influences the way in which a protein folds?

Answer 19

• Chemical properties of the amino acids
• Physical properties of the amino acids

Question 20

How can amino acids be classified based on their chemical properties?

Answer 20

• Hydrophobic / Hydrophilic
• Polar / Non-polar
• Acidic / Basic / Neutral

Question 21

How can amino acids be classified based on their physical properties?

Answer 21

Aliphatic / Aromatic

Question 22

What are amino acid residues?

Answer 22

Amino acid residues are what remains of an amino acid after it has been joined by a peptide bond to form a protein

Question 23

How do pK_a values vary across acidic and basic amino acids?

Answer 23

- Basic amino acids:

I. Positively charged R groups

II. Higher pK_a values (6.0 - 12.5)

- Acidic amino acids:

I. Negatively charged R groups

II. Lower pK_a values (2.8 - 4.3)

Question 24

Illustrate the relationship between pK values and pH in terms of amino acids

Answer 24

• pH of the solution < pK value of amino acid = R group is protonated
• pH of the solution > pK value of amino acid = R group is deprotonated

Question 25

What is meant by the isoelectric point of proteins?

Answer 25

**Isoelectric point (pI) of proteins:** the pI of a protein is the pH at which there is no overall net charge

Question 26

How do pI values vary across acidic and basic proteins?

Answer 26

- **Basic proteins** have a pI \> 7 and contain many positively charged (basic) amino acids - **Acidic proteins** have a pI \< 7 and contain many negatively charged (acidic) amino acids

Question 27

Illustrate the relationship between pI values and pH in terms of proteins

Answer 27

- If the pH \< pI then the protein is **protonated** - If the pH \> pI then the protein is **deprotonated**

Question 28

What are conjugated proteins?

Answer 28

Conjugated proteins are proteins which have other chemical components covalently linked in addition to amino acids *e.g. haemoglobin*

Question 29

Identify 5 biochemical roles of proteins

Answer 29

- **Catalysts** *e.g. enzymes* - **Transporters** *e.g. haemoglobin carries O₂* - **Structural support** *e.g. collagens in skin and bone* - **Immune protection** *e.g. immunoglobulins* - **Receptors** *e.g. for hormones, neurotransmitters, etc*

Question 30

Identify the 4 different components to protein structure

Answer 30

Question 31

Describe the primary structure of the protein

Answer 31

**Primary structure** is the linear amino acid sequence of the polypetide chain

Question 32

Describe the secondary structure of the protein

Answer 32

**Secondary structure** is the local spatial arrangement of polypeptide backbone consisting of alpha helixes and beta pleated sheets

Question 33

Which type of bond stabilises the secondary structure of a protein?

Answer 33

H₂ bonds

Question 34

Describe the tertiary structure of the protein

Answer 34

**Tertiary structure** is the overall 3D configuration of the protein

Question 35

Describe the quaternary structure of the protein

Answer 35

**Quaternary structure** is the association between different polypeptides to form a multi-subunit protein

Question 36

Identify the 4 interactions which stabilise the tertiary structure

Answer 36

- Disulphide bonds - Hydrophobic interactions - Hydrogen bonds - Ionic interactions

Question 37

Which bonds hold subunits together in the quaternary structure of the protein?

Answer 37

**Non-covalent interactions:** - Hydrogen bonds - Ionic bonds - Hydrophobic interactions

Question 38

How do subunits function in the quaternary structure of proteins?

Answer 38

- Subunits can function **independently** - Subunits can function **cooperatively** *e.g. haemoglobin*

Question 39

Describe the role and structure of fibrous proteins and include an example

Answer 39

- **Role**: support, shape, protection - **Structure**: single type of repeating secondary structure, forms long strands or sheets - **Examples**: collagen & keratin

Question 40

Describe the role and structure of globular proteins and include an example

Answer 40

- **Role**: catalysis, regulation, transport - **Structure**: several types of secondary structure - **Examples**: myoglobin, haemoglobin, carbonic anhydrase

Question 41

Identify the 2 types of secondary structures found in globular proteins

Answer 41

- Motifs - Domains

Question 42

Describe the 2 types of secondary structures found in globular proteins

Answer 42

- **Motifs** which are folding patterns containing 1/more elements of secondary structure - **Domains** which are the parts of a polypeptide chain that fold into a distinctive shape

Question 43

How do membrane proteins fold?

Answer 43

**Membrane proteins** fold to express hydrophobic amino acids on the exterior cell surface and hydrophilic amino acids on the interior forming channels

Question 44

How do water soluble proteins fold?

Answer 44

In **water soluble proteins,** polypeptide chains fold so the hydrophobic side chains are buried and polar and the charged side chains are on the cell surface

Question 45

Describe the relative amount of amino acids in the following: - Peptides/oligopeptides - Polypeptides/proteins

Answer 45

- **Peptides/oligopeptides:** few amino acids in length - **Polypeptides/proteins:** many amino acids in length