Introduction to Protein Structures: Primary, Secondary, Tertiary and Quarternary

Proteins are vital to nearly every function in living organisms, from speeding up reactions as enzymes to giving cells their structure and strength. But have you ever wondered how their unique structures enable them to do so much? In this blog, we’ll break down the four levels of protein structure—primary, secondary, tertiary, and quaternary—and show how each level plays a key role in determining the specific function of a protein. Let’s jump into it!

Primary Structure: The Foundation

The primary structure of a protein refers to the specific sequence of amino acids in a polypeptide chain. 

It’s essential to understand that the order, or sequence, of these amino acids determines how the protein will function. Each amino acid in the chain is linked to the next by peptide bonds—strong covalent bonds that form between the carbon atom in the carboxyl group of one amino acid and the nitrogen atom in the amine group of another. 

These bonds are created through condensation reactions, where water is removed during the bonding process. This sequence is the foundation upon which all other levels of protein structure are built.

An illustration of a Peptide Bond

Secondary Structure

The secondary structure of a protein involves the simple folding of the polypeptide chain. This folding is stabilised by hydrogen bonds, which form between the amine group (specifically the hydrogen) and the carboxyl group (which contains oxygen) in the backbone of the amino acids. 

These bonds create two main structural motifs: alpha helices and beta-pleated sheets. The hydrogen bonds play a critical role in holding these structures together, giving the protein its initial shape and laying the groundwork for more complex folding in higher levels of protein structure.

An illustration of a Hydrogen bond in the secondary structure of a protein

Tertiary Structure

The tertiary structure of a protein is crucial as it determines the specific 3D shape of the protein, which is essential for its function. This 3D shape is especially important for proteins like enzymes, where the structure of the active site must be complementary to the substrate. 

Other proteins, such as hormones, receptors, antigens, and antibodies, also rely on having the correct 3D shape to perform their functions.

The tertiary structure is held together by three main types of bonds: hydrogen, ionic, and disulfide. The strongest disulfide bonds form between sulfur atoms in the R groups of two cysteine amino acids. 

While ionic bonds are weaker than disulfide bonds, they can still be broken by extreme temperatures or pH changes. Hydrogen bonds are the weakest and most susceptible to breaking with temperature changes or pH fluctuations, which can lead to protein denaturation.

An illustration of Hydrogen, Ionic and Disulfide bonds in the tertiary structure of a protein

Quaternary Structure

The quaternary structure is the fourth and final level of protein structure. It refers to proteins that consist of more than one polypeptide chain. This could mean two or more polypeptide chains, but it doesn’t necessarily mean four chains, even though proteins like haemoglobin and antibodies happen to have four. The number of chains can vary, and the key point is that the protein is made up of multiple polypeptide chains.

The same bonds that hold the tertiary structure together—hydrogen bonds, ionic bonds, disulfide bonds, and hydrophobic/hydrophilic interactions—also maintain the quaternary structure.

Exam-style practice questions and tips

1. Explain why the specific tertiary structure of a protein is dependent on the primary structure of the polypeptide chain 

The primary structure refers to the sequence of amino acids in a polypeptide chain. Each amino acid has a unique R group, and the sequence of these R groups determines the way the protein folds into its tertiary structure. The bonds that hold the tertiary structure together, such as hydrogen, ionic, and disulfide bonds, form between these R groups. If the sequence of amino acids changes, the sequence of R groups will also change, altering the positions of these bonds and the resulting 3D shape of the protein.

Tip: Always name at least one bond (e.g., hydrogen, ionic, or disulfide) when describing protein structure to ensure full marks in your answer.

2. Describe how a peptide bond is formed between two amino acids to form a dipeptide (2 marks)

A peptide bond forms through a condensation reaction, where a molecule of water is removed as the bond is created. Specifically, the bond forms between the carbon in the carboxyl group of one amino acid and the nitrogen in the amine group of another amino acid.

Tip: Make sure to mention both where the bond forms (between carbon and nitrogen) and the condensation reaction to get full marks.

3. Describe how the secondary structure of a polypeptide is produced by bonds between amino acids (2 marks)

The secondary structure is primarily created by hydrogen bonds that form between the amine and carboxyl groups of the amino acids. These bonds cause the chain to fold into specific motifs, such as alpha helices and beta-pleated sheets.

[add image illustrating bond between amino acids and carboxyl group]

Tip: Name the types of structures created (alpha-helix and beta-pleated sheet) when talking about a secondary structure for extra clarity.

4. Two proteins have the same number and type of amino acids but different tertiary structures. Explain why (2 marks)

Even though the proteins have the same amino acids, they can have different primary structures, meaning the amino acids are arranged in a different sequence. This causes the bonds that hold the tertiary structure together, such as ionic or hydrogen bonds, to form in different places, resulting in different 3D shapes.

Tip: Always name at least one bond, such as ionic, hydrogen, or disulfide, when discussing tertiary structure to strengthen your answer.

Conclusion

Understanding protein structures at every level is key to appreciating their role in the body. From the primary sequence of amino acids to the complex quaternary structures, each level contributes to shaping the final protein and enabling it to carry out its specific function. Whether it's enzymes speeding up reactions or haemoglobin transporting oxygen, the structure of a protein defines its ability to support life. By grasping these levels, we can better understand how proteins are essential to health and biological processes.