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How is progressing through higher order protein structures like crafting an essay? In this lesson, you’ll explore everything from quaternary structures to denaturation as we show how the different structures are intertwined.

Higher Order of Protein Structure

In this lesson, we’ll be learning about primary, secondary, tertiary and quaternary structure of proteins, but first, let’s take a little detour and talk about writing.What does writing have to do with biochemistry? Well, let’s think about this for a second.

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Three amino acids can come together to form a tripeptide.
Tripeptide

So let’s say you need to write a story and your story will be made of several paragraphs. Now when you go to write a paragraph, you don’t just think of random letters and have them magically assemble into your finished paragraph, do you? Instead, you take your letters and use them to create words.

There are different types of words, right? So these different types of words can be things like nouns, pronouns, adverbs and verbs, and all of these different things can be put together to form sentences. After you have sentences, these sentences can come together to form a paragraph that makes sense for your story.Now in the case of proteins, it’s not exactly the same, but it’s pretty similar. As we know, amino acids can come together to form peptides. These can be very short, like dipeptides that consist of two amino acids, tripeptides, which consist of three amino acids, and polypeptides, which is anything from there up to about 30 amino acids. Finally, amino acids can come together to form proteins.

Primary Structure

Amino acids just don’t kind of come together and hope that they make the right protein; instead, there’s something called the primary structure, which tells us the order of amino acids in a protein.

This is dictated by our DNA, but we don’t need to worry about that right now. We need to know that the primary structure of a protein is a list of the amino acids in the protein, from the n-terminus with the free amino group, to the c-terminus with the free carboxillic acid group.So at this point we have the primary structure of the protein well in hand. We know the order of the amino acids, but we don’t know how they arrange with respect to one another like the words in a sentence would.

Secondary Structure

A random coil is a type of secondary structure.
Random Coil

This is where the secondary structure comes in. The secondary structure is a repetitive 3-D structure of a protein.

These are things that people often come into contact with when they’re looking at protein structures. Secondary structures are common among proteins, so different proteins will have the same types of secondary structures. The most common one of these is called the alpha helix. The alpha helix is the secondary structure where the protein coils because there are hydrogen bonds between the backbones of their amino acids.

The alpha helix gets its coil shape from hydrogen bonds.
Alpha helix

So if we look at this example, we can see that there are hydrogen bonds forming between the amine nitrogens and the carbonyl oxygens in different amino acids.

Now when we say backbone, what we mean are the peptide bonds in addition to the nitrogen in the amine, the carbon on which the side group sits and the carbonyl carbon. And as you can see, in the case of this alpha helix, it looks like a coil, hence the name ‘helix.’Another common secondary structure is the beta sheet, or the beta pleated sheet. The beta sheet is a secondary structure where the backbones of different strands of the amino acids (meaning not the side chain part) are held together by hydrogen bonds between the amine nitrogen and the carbonyl oxygen. These form a flattened region in the protein.Finally, there’s the random coil.

As you might imagine by its name, it’s an unstructured peptide chain. So this is what happens when there isn’t hydrogen bonding between the backbone of the protein and it’s just floating around out in space kind of flexibly. Think of it sort of like a protein piece of spaghetti.

Tertiary Structure

So just like we take words and put them into sentences, we can take the primary and secondary structures of a protein and they can interact to form the tertiary structure.

Now the tertiary structure is the complete 3-D structure of a protein, or peptide, including all of its atom arrangements because they tend to stay fairly stationary.So when we look at hemoglobin, the protein that carries oxygen throughout our bodies, we find that it’s made of two alpha protein subunits and two beta protein subunits, so it’s made of four different pieces.

The hemoglobin beta subunit is made up of many amino acids.
 Hemoglobin beta subunit

Let’s just focus on one of them for right now: the hemoglobin beta subunit.

We can see here that the subunit is made up of many amino acids in its primary structure. These amino acids come together to form several alpha helices, which come together to form its tertiary structure.You may also notice a funky little group sticking in the middle of the hemoglobin that has four sides. This is the heme group and is what carries the oxygen around our bodies. Just a fun fact!So like we said, hemoglobin has two alpha subunits and two beta subunits. So how do those come together? Just like sentences don’t typically stand by themselves when you’re writing a story, the proteins don’t always stand alone either.

Some of them come together to form larger groups of proteins.

Quaternary Structure

This is called the quaternary structure. This is the complete 3-D structure of a protein that contains multiple peptides or proteins. In this case, hemoglobin is made up of four different proteins.

You’ll notice that all of these subunits come together to form a large, donut-shaped molecule.

The quaternary structure of a protein, such as hemoglobin, consists of multiple peptides.
Quaternary Hemoglobin Structure

Sickle Cell Anemia

To give you an idea of how important and interrelated primary, secondary, tertiary and quaternary structures of proteins can be, we’ll look at sickle cell anemia.Sickle cell anemia is a disease that happens when there’s a mutation in the beta subunit of hemoglobin. In people, this causes a very painful disease where their red blood cells become sickle shaped, instead of being normal round red blood cells, and don’t work as well.

This single change in the primary structure causes changes in the secondary, tertiary and quaternary structures that result in a change in the overall shape of the protein. Sickle cell hemoglobin behaves normally when oxygen is bound to it, but when oxygen is not bound to it, it can form large polymers of protein where all the subunits of many different hemoglobin molecules come together and form a very long strand of sickle cell hemoglobin. This is what causes the cells to become sickle shaped.

Denaturation

An egg becomes solid when fried because its proteins undergo denaturation.
Egg Becomes Solid Due to Denaturation

Now generally, proteins like to exist in their most stable form and they actually are very stable and it’s difficult to make them lose their structure. The way to make them lose structure is to make them undergo something called denaturation, which is the breakdown of the secondary, tertiary, and quaternary structures of protein by heat or chemical treatment.

So if you treat a protein with a lot of acid, or you cook it, then it takes the protein, breaks the beta sheets and helices and turns the entire protein into a random coil.This is why an egg suddenly becomes solid when you fry it. When you first crack an egg, all of its proteins are in their natural state. As you heat it, the proteins break down into random coils and these long strands come together and have intermolecular forces with each other, causing them to solidify into your delicious fried egg.

Lesson Summary

To summarize, we’ve discussed that much like writing a story, proteins come together in a specific way.

Primary structures are like words; they’re not made of random amino acids, but are made of specifically ordered amino acids, just as words are made of specifically ordered letters.The secondary structure, which is the repetitive 3-D structure of a protein, comes in three different flavors: the alpha helix, the beta sheet and the random coil. These are sort of like different types of words that you can put together in the case of an essay or a story to make a sentence.The tertiary structure is the complete 3-D structure of a single protein or a peptide including all of its atom arrangements. Finally, just as sometimes sentences aren’t off by themselves but are part of paragraphs, the quaternary structure is the complete 3-D structure of a protein that has multiple peptide or protein parts.In addition, we’ve learned that denaturation, which is the breakdown of the secondary, tertiary and quaternary structures of proteins, can happen by heating or chemical treatment of a protein, and leaves the primary structure of a protein intact.

Learning Outcomes

When you are done, you should be able to:

  • Name and describe the four protein structures
  • Identify the three different types of secondary structure
  • Explain how proteins can be forced to lose their structure

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