Proteins (VCE SSCE Chemistry): Revision Notes

Proteins

Introduction to proteins

Proteins are large biological molecules built from chains of amino acid units. They perform essential functions throughout the body, including:

• Acting as hormones that regulate biological processes
• Providing structural components in cell membranes, muscles, hair and feathers
• Functioning as antibody molecules in the immune system
• Transporting substances across cell membranes or around the body
• Serving as enzymes that speed up specific biochemical reactions

Primary structure of proteins

The primary structure of a protein refers to the number, type, and sequence of amino acid units that make up the protein chain. This sequence is extremely important because it determines the protein's ultimate function.

Amino acids join together through peptide links (also called peptide bonds, represented as —CONH—) to form a polypeptide chain. These peptide links form when the carboxyl group ($-COOH$) of one amino acid reacts with the amino group ($-NH_{2}$) of another amino acid, releasing a water molecule.

The diagram above shows part of the glycinin protein found in soybeans. Notice how the peptide links (highlighted in blue) connect each amino acid unit to the next. Each protein has a precise chemical composition and amino acid sequence, resulting in a unique three-dimensional shape.

Secondary structure of proteins

The secondary structure of a protein describes the coiling and pleating of sections of the polypeptide chain. These regularly arranged sections are stabilised by hydrogen bonds that form between different parts of the molecule.

Hydrogen bonding in secondary structure

Hydrogen bonds form between the polar $-NH$ group in one peptide link and the polar $-C=O$ group in another peptide link at regular intervals along the chain.

The hydrogen atom in the $-NH$ group carries a partial positive charge ($\delta^+$), while the oxygen atom in the $-C=O$ group carries a partial negative charge ($\delta^-$). The attraction between these opposite charges creates the hydrogen bond.

α-helices

An α-helix is a spiral or spring-like structure formed when a polypeptide chain coils due to hydrogen bonding. Keratin, the protein found in hair and wool fibres, has an α-helical structure.

In keratin, hydrogen bonds form between the $-NH$ group of one peptide link and the $-C=O$ group of a peptide link four amino acid units along the chain. This extensive hydrogen bonding throughout the chain causes it to coil into the characteristic helical shape.

β-pleated sheets

A β-pleated sheet forms when hydrogen bonds occur between peptide links in different sections of the polypeptide chain, causing these sections to line up parallel to each other.

The repeating structure of the protein backbone ($-N-C-C-N-C-C-N-C-C-$) allows hydrogen bonds to form at regular intervals between adjacent sections. This creates a sheet-like structure with a pleated appearance.

Silk is an excellent example of a protein with a β-pleated sheet structure. The polypeptide chains in silk are mainly composed of the amino acids glycine, alanine, and serine.

Notice that every second R group (side chain) in silk is simply a hydrogen atom ($H$). These small side chains allow sections of the protein molecule to align closely together, enabling hydrogen bonds to form between adjacent sections and creating the β-pleated sheets that give silk its characteristic strength and texture.

Acid-base properties of amino acids

To understand how proteins fold into their final shapes and how pH affects protein structure, we need to understand the acid-base properties of amino acids.

Zwitterion formation

Amino acids contain both polar amine ($-NH_{2}$) and carboxyl ($-COOH$) functional groups. This gives them special properties in solution:

• The $-NH_{2}$ group can act as a base, accepting a proton ($H^{+}$) to become $-NH_{3}^{+}$
• The $-COOH$ group can act as an acid, donating a proton to become $-COO^{-}$

In aqueous solution, an amino acid can exist as a zwitterion – a dipolar ion that contains both a positive charge (on the amino group) and a negative charge (on the carboxyl group). Although the zwitterion has charged regions, its overall charge is neutral because the positive and negative charges balance each other.

Effect of pH on amino acid structure

Because amino acids can act as both acids and bases, different chemical forms can exist in equilibrium in solution. The predominant form depends on the pH of the solution.

• At low pH (acidic conditions): The presence of excess $H^{+}$ ions favours the formation of a cation (positively charged ion). Both the amino and carboxyl groups are protonated.
• At intermediate pH: The zwitterion form predominates, with a protonated amino group ($-NH_{3}^{+}$) and a deprotonated carboxyl group ($-COO^{-}$). The overall charge is neutral.
• At high pH (alkaline conditions): The presence of excess $OH^{-}$ ions favours the formation of an anion (negatively charged ion). Both groups are deprotonated.

Effect of R groups on acid-base properties

The R group (side chain) of an amino acid can significantly influence its acid-base behaviour. If the R group contains functional groups with acid-base properties, additional charged forms can exist.

Acidic amino acids: Amino acids like aspartic acid have R groups containing carboxyl groups. At pH 12, aspartic acid exists predominantly as an ion with a charge of 2− because both carboxyl groups (the one in the backbone and the one in the R group) are deprotonated.

Basic amino acids: Amino acids like lysine have R groups containing amino groups. At pH 2, lysine exists predominantly as an ion with a charge of 2+ because both amino groups (the one in the backbone and the one in the R group) are protonated.

Tertiary structure of proteins

The tertiary structure of a protein is its overall three-dimensional shape, formed by the folding of its secondary structures (α-helices and β-pleated sheets) in space. The protein can twist and fold back over itself to create a unique shape that is essential for its biological function.

The diagram above shows myoglobin, a protein with a complex tertiary structure. Notice how the polypeptide chain folds into a compact, globular shape.

Factors influencing tertiary structure

The R groups (side chains) of amino acids play a crucial role in determining the final three-dimensional shape of a protein. Several factors contribute to this folding:

• Size of R groups: Some R groups, like that in phenylalanine, are relatively large and bulky
• Polarity: Some R groups contain polar functional groups
• Charge: Depending on pH, some R groups can become positively or negatively charged
• Hydrophobic nature: Non-polar R groups tend to fold towards the interior of protein molecules, away from water

Types of bonding in tertiary structure

Five main types of interactions between R groups stabilise the tertiary structure of proteins:

1. Hydrogen bonds

Form between R groups containing $-O-H$, $-N-H$, or $-C=O$ groups. These are similar to the hydrogen bonds in secondary structure but occur between different parts of the folded chain.

2. Dipole-dipole interactions

Occur between any polar R groups, such as those containing $-S-H$, $-O-H$, or $-N-H$ groups. The partial charges on these groups attract each other.

3. Ionic interactions

Form between R groups with opposite charges, such as between an $-NH_{3}^{+}$ group on one amino acid and a $-COO^{-}$ group on another amino acid.

4. Covalent cross-links (disulfide bridges)

Form when two cysteine amino acids come close together. The thiol groups ($-SH$) on their R groups react to form a disulfide bridge ($-S-S-$). These are the strongest interactions in protein tertiary structure.

5. Dispersion forces

Occur between any non-polar R groups. Although individually weak, the cumulative effect of many dispersion forces can be significant, especially in proteins with many non-polar amino acids.

Quaternary structure of proteins

Some proteins are composed of two or more polypeptide chains that interact together. When multiple chains and/or non-protein molecules combine to produce a larger, more complex functional unit, this is called the quaternary structure.

Haemoglobin: an example of quaternary structure

Haemoglobin is the oxygen-transporting protein found in red blood cells. It provides an excellent example of quaternary structure.

The haemoglobin molecule consists of four distinct subunits (shown in different colours above). Each subunit contains:

• A polypeptide chain (called globin) that is coiled into α-helices and folded into a tertiary structure
• An oxygen-binding site called a haem group (shown in light blue)
• One iron atom ($Fe^{2+}$) within each haem group (shown in green)

Haemoglobin transports oxygen around the body by binding one oxygen molecule ($O_{2}$) to the iron atom in each haem group. Since there are four haem groups, one haemoglobin molecule can transport four oxygen molecules.

Summary of protein structure levels

The following table summarises the four levels of protein structure:

Level of bonding	Effect of bonding	Types of bonding
Primary	Sequence of amino acids in the main chain	Covalent bonds (peptide links)
Secondary	Coiling or pleating of the protein chain	Hydrogen bonding between $-N-H$ and $-C=O$ on different parts of the molecule
Tertiary	Overall three-dimensional shape of the protein	Formed by a variety of bond types between the R groups on different parts of the protein molecule
Quaternary	Some proteins contain more than one peptide chain and form a more complex unit	Dispersion forces or other bonds between molecules