Protein Structure

Proteins are biological molecules with complex structures built of amino acids. Based on the sequence of these amino acids and the complexity of the structures, we can differentiate four protein structures: primary, secondary, tertiary, and quaternary.

Amino acids: basic units of proteins

In the article Proteins, we have already introduced amino acids, these vital biological molecules. However, why not repeat what we already know to better understand the four structures of proteins? It is, after all, said that repetition is the mother of all learning.

Amino acids are linked with peptide bonds during a chemical reaction called condensation, forming peptide chains. With more than 50 amino acids joined together, a long chain called a polypeptide chain (or a polypeptide) is formed. Have a look at the figure below and notice the structure of amino acids.

Fig. 1 - Structure of amino acids, the basic units of protein structure

With our knowledge refreshed, let’s see what the four structures are all about.

Primary protein structure

The primary protein structure is the sequence of amino acids in a polypeptide chain. This sequence is determined by the DNA, more precisely by specific genes. This sequence is essential because it affects both the shape and the function of proteins. If only one amino acid in the sequence is changed, the shape of the protein changes. Moreover, if you remember that the shape of biological molecules affects their functions, you can conclude that the shape of proteins also changes their function. You can read more about the importance of DNA in creating a specific sequence of amino acids in our article on protein synthesis.

Fig. 2 - Primary structure of proteins. Notice the amino acids in the polypeptide chain

Secondary protein structure

The secondary protein structure refers to the polypeptide chain from the primary structure twisting and folding in a certain way. The degree of the fold is specific to each protein.

The chain, or parts of the chain, can form two different shapes:

• α-helix
• β-pleated sheet.

Proteins may have only an alpha-helix, only a beta-pleated sheet, or a mix of both. These folds in the chain will happen when hydrogen bonds form between amino acids. These bonds provide stability. They form between a positively charged hydrogen atom (H) of the amino group -NH2 of one amino acid and a negatively charged oxygen (O) of the carboxyl group (-COOH) of another amino acid.

Suppose you have gone through our article on biological molecules, covering different bonds in biological molecules. In that case, you will remember that hydrogen bonds are weak on their own, but provide strength to molecules when in large quantities. Still, they are easily broken.

Fig. 3 - Parts of the chain of amino acids can form shapes called α-helix (coil) or β-pleated sheets. Can you spot these two shapes in this structure?

Tertiary protein structure

In the secondary structure, we have seen that parts of the polypeptide chain twist and fold. If the chain twists and folds even further, the whole molecule gets a specific globular shape. Imagine you took the folded secondary structure and twisted it further so that it starts folding into a ball. This is the tertiary protein structure.

The tertiary structure is the overall three-dimensional structure of proteins. It is another level of complexity. You can say that the protein structure has “levelled up” in complexity.

In the tertiary structure (and in the quaternary, as we will see later), a non-protein group (prosthetic group) called a haem group or haem can be connected to the chains. You might come across the alternative spelling of heme, which is US English. The haem group serves as a “helper molecule” in chemical reactions.

Fig. 4 - Structure of oxy-myoglobin as an example of the tertiary protein structure, with a haem group (blue) connected to the chain

As the tertiary structure is formed, bonds other than peptide bonds form between amino acids. These bonds determine the shape and stability of the tertiary protein structure.

• Hydrogen bonds: These bonds form between the oxygen or nitrogen and hydrogen atoms in R groups of different amino acids. They are not strong even though there are many of them present.

• Ionic bonds: Ionic bonds form between the carboxyl and amino groups of different amino acids and only those groups that do not already form peptide bonds. In addition, amino acids need to be close to one another for ionic bonds to form. Like hydrogen bonds, these bonds are not strong and are easily broken, usually due to the change in pH.

• Disulfide bridges: These bonds form between amino acids that have sulphur in their R groups. The amino acid in this case is called cysteine. Cysteine is one of the important sources of sulphur in human metabolism. Disulfide bridges are much stronger than hydrogen and ionic bonds.

Quaternary protein structure

Quaternary protein structure refers to an even more complex structure consisting of more than one polypeptide chain. Each chain has its own primary, secondary, and tertiary structures and is referred to as a subunit in the quaternary structure. Hydrogen, ionic, and disulfide bonds are present here as well, holding the chains together. You can learn more about the difference between tertiary and quaternary structures by looking at haemoglobin, which we will explain below.

Structure of haemoglobin

Let’s look at the structure of haemoglobin, one of the essential proteins in our bodies. Haemoglobin is a globular protein that transfers oxygen from the lungs to cells, giving the blood its red colour.

Its quaternary structure has four polypeptide chains interlinked with the chemical bonds mentioned. The chains are called alpha and beta subunits. Alpha chains are identical to one another, and so are the beta chains (but are different from alpha chains). Connected to these four chains is the haem group that contains the iron ion to which oxygen binds. Take a look at the figures below for a better understanding.

Fig. 5 - The quaternary structure of haemoglobin. The four subunits (alpha and beta) are two different colours: red and blue. Notice the heam group attached to each unit

Fig. 6 - The chemical structure of haem (heme). Oxygen binds to the central iron ion (Fe) in the bloodstream

The relationships between primary, tertiary, and quaternary structures

When asked about the importance of protein structure, remember that the three-dimensional shape affects protein function. It gives each protein a specific outline, which is important because proteins need to recognise and be recognised by, other molecules to interact.

Remember fibrous, globular, and membrane proteins? Carrier proteins, one type of membrane protein, usually carry only one type of molecule, which bind to their “binding site”. For instance, glucose transporter 1 (GLUT1) carries glucose through the plasma membrane (the cell surface membrane). If its native structure were to change, its effectiveness to bind glucose would decrease or be lost entirely.

The sequence of amino acids

Moreover, even though the 3-D structure does indeed determine the function of proteins, the 3-D structure itself is determined by the sequence of amino acids (the primary structure of proteins).

You might ask yourself: why does a seemingly simple structure play such a vital role in the shape and function of some rather complex ones? If you remember reading about the primary structure (scroll back up in case you’ve missed it), you know that the protein’s whole structure and function would change should only one amino acid be omitted or swapped for another. This is because all proteins are “coded”, meaning they will function properly only if their constituents (or units) are all present and all fitting or that their “code” is correct. The 3-D structure is, after all, many amino acids joined together.

Building the perfect sequence

Imagine you are building a train, and you need specific parts so that your carriages link to a perfect sequence. If you use the wrong type or do not use enough parts, the carriages would not link up correctly, and the train would work less effectively or derail altogether. If that example is way out of your expertise, as you might not be building a train at the moment, think of using hashtags on social media. You know you need to put the # first, followed by a set of letters, with no space between the # and the letters. For instance, #lovebiology or #proteinstructure. Miss one letter, and the hashtag wouldn’t work exactly how you want it to.

Levels of protein structure: diagram

Fig. 7 - Four levels of protein structure: primary, secondary, tertiary, and quaternary structure