Quaternary Structure - Online Tutor, Practice Problems & Exam Prep

Quaternary protein structure involves multiple polypeptide chains, known as subunits, which can be identical (homodimers) or different (heterodimers). Interactions between subunits primarily occur through non-covalent interactions, such as the hydrophobic effect, although disulfide bridges can provide covalent links. For example, hemoglobin is a heterotetramer with four non-identical subunits, while insulin consists of two subunits linked by disulfide bridges. Understanding these interactions is crucial for grasping protein functionality and dynamics in biological systems.

Quaternary Structure

So at this point, we've talked about primary protein structure all the way up through tertiary protein structure, and we've also talked about denaturation, the Anfinsen experiment, protein folding, and chaperone proteins. So you guys know a lot about protein structure. And in this video, we're going to continue to talk about protein structure as we talk about our 4th and final level of protein structure, quaternary protein structure. So quaternary protein structure is just referring to a single protein complex consisting of multiple polypeptide chains. And so each of the polypeptide chains that are part of this larger protein complex is referred to as a subunit. And so a subunit is really just any polypeptide chain that assembles with other polypeptide chains. And so, when they assemble with other polypeptide chains, that automatically forms quaternary structure. And so subunits can either be identical or homo, or they could be different or hetero. And so, what you'll see is that the terms dimers, trimers, and tetramers consist of respectively 2, 3, and 4 subunits. And so in our example below, we'll be able to distinguish between these terms. And what you'll see is that in our first block over here on the left, what we have are dimers. And the reason that we know that these are dimers is because we can see that there are 2 polypeptide chains or 2 subunits that are complexing or assembling together to create a single unit. So this is a single complex that has 2 polypeptide chains or 2 subunits, and this is a single complex that has 2 subunits as well. Now notice that these 2 subunits that are over here, that they are identical, and because they're identical, that means that they are going to be homodimers. These are homodimers. And these 2 subunits over here, because they are not identical, they're different from one another, that makes them heterodimers. And so, over here in our middle block, what you'll see is that we've got 3 subunits, And so with this single protein complex, we've got 3 subunits that makes it a trimer. So this is a trimer. And again, because all 3 of these subunits are not identical, we've got 3 different subunits, that technically makes it a heterotrimer. And so over here in our 4th and final block, what we have is, a single protein complex, but it has 4 subunits in it. And so because it has 4 subunits, that makes it a tetramer, Tetra meaning 4. And so with this tetramer, because not all 4 of the subunits are identical, that technically makes it a heterotetramer. So you only call it homo if it has all identical subunits. If it has at least one subunit that is different, it's automatically going to be a hetero structure. And so, this concludes our lesson on quaternary structure and these terminologies, and we'll be able to apply these concepts in our practice video. So, I'll see you guys in that practice video.

Hemoglobin, a four-subunit protein, contains only two different types of subunits and is therefore a:

• A. Dimer.
• B. Heterodimer.
• C. Homotetramer.
• D. Heterotetramer.

Quaternary Structure

Now that we've introduced quaternary structure, we could talk about quaternary structure interactions, or the interactions that take place between subunits and allow the subunits to stick together in a protein with quaternary structure. And it turns out that subunits mainly interact with each other via non-covalent interactions, such as, for instance, the hydrophobic effect. Now, although they mainly interact via non-covalent interactions, there are some exceptions and of course, disulfide bridges can covalently link subunits together. But recall that disulfide bridges form between 2 cysteine residues, specifically the R groups of the cysteine residues. So you could have 2 cysteine residues on separate subunits and then those subunits are linked together via the R groups of the cysteines in the disulfide bridge. But it's really important to keep in mind that subunits are not linked via their backbones. So backbones of subunits are not covalently linked and that's very important to keep in mind for subunits. Now because these subunits are so closely associated with one another, they're literally right up on each other, a conformational change in one subunit can actually alter the other subunits. And so, if one subunit makes a conformational change, that might induce the other subunit to also make a conformational change even though they are not linked via their backbones. And so, we'll see examples of that when we talk about hemoglobin in more detail later down the line in our course.

Now, in our example below, what you'll see is that we've got hemoglobin over here on the left and we've got insulin on the right. And we already know that hemoglobin is a heterotetramer, which means that it's got 4 subunits that are not identical. And so down here, what we can say is that it's got 4 subunits. And notice that these 4 subunits are color-coded with 4 different colors in this image right here. And so these 4 subunits, they actually only complex with each other and interact with each other via non-covalent interactions. It turns out that there are 0 disulfide bonds holding these separate subunits together. And so, hemoglobin is a classic example of showing how most of the interactions between subunits are non-covalent. Now over here with insulin, what you'll see is that we've got 2 separate polypeptide chains or 2 separate subunits. We've got the alpha chain, which is this chain here in purple, and then we've got the beta chain or the B chain, which is this chain over here in pink. And so the alpha chain or the A chain up here has a total of 21 amino acids residues and the B chain has a total of 30 amino acid residues. And what you'll see is that these 2, subunits of insulin, notice that they have disulfide bridges. So they are highlighted here. So, you can see that there is a disulfide bridge here, but this one forms between 2 cysteine residues on the same A chain. And so this one's not linking the 2 subunits, but these other disulfide bridges that are formed here and here in light blue, these 2 are forming between cysteine residues on the 2 separate subunits, and so they are linking the 2 subunits covalently via the R groups. And again, the backbones are not covalently linked together. So they both still have their free amino and carboxyl groups of both subunits. And so over here, what we have is a different depiction of the same insulin molecule. So you can see this blue portion here corresponds with this blue alpha chain over here, and then this red chain over here corresponds with the red beta chain down here. And so you can see that these yellow bonds here are the disulfide bridges. So there are a total of 3 disulfide bridges. One of them forms between the same chain, but 2 of them form between the separate subunits. And so, for the insulin molecule, what we'll see is that it's got a total of 2 subunits and it's got a total of 3 disulfide bonds. 2 of them are linking the subunits together whereas one of them is an intra-chain disulfide bond forming within the same subunit. And so, this concludes our lesson on quaternary structure interactions and we'll be able to get some practice on all of these concepts in our practice video. So I'll see you guys there.

Which of the following statements about protein structure is correct?

• A. The α-helix is stabilized primarily by ionic interactions between amino acid R groups.
• B. Disulfide bond formation can only form between adjacent cysteine residues in a sequence.
• C. The stability of quaternary structure in all proteins is primarily due to covalent bonds between subunits.
• D. The denaturation of a protein always leads to irreversible loss of secondary & tertiary structure.
• E. Quaternary subunits complex primarily through hydrophobic interactions between chains.

Match each level of protein structure to the appropriate real-world description.

_____ Primary Structure. _____ Secondary structure. _____ Tertiary structure. _____ Quaternary structure.

So this practice problem wants us to match each level of protein structure to the appropriate real world description down below. And so, option a here says, myoglobin folds so that most of its hydrophobic residues are interior and its hydrophilic ones are exterior. And so, because this is referring to the overall folding and the overall three-dimensional shape of myoglobin, this is referring to the tertiary structure, which again recall that tertiary structure refers to the overall three-dimensional shape. And so what we can do is we can put in option a over here and cross off a from our list. Now, b says the preproinsulin polypeptide is 110 amino acids long, and so the number of amino acids is part of the amino acid composition, and so the composition of amino acids is part of the primary protein structure. And so what that means is that b here, we can list as primary structure and cross it off our list. Now, c says, malate dehydrogenase, a citric acid cycle enzyme, is a homooctamer composed of 8 identical subunits. Anytime you see subunits, you should be thinking about quaternary structure. Indeed, because this is saying that we have a homooctamer here, this is referring to the quaternary structure, so we can put c here and cross c off our list. And then, of course, that means that our last option, d, has to be referring to secondary structure. And what you can see is that it says proteins that use NADH as a cofactor contain an NADH binding site composed of antiparallel beta sheets. We know that antiparallel beta sheets are a type of secondary structure, so that's why it's d. And so this concludes this practice problem and I'll see you guys in our next video.

Here’s what students ask on this topic:

What is quaternary protein structure and how does it differ from tertiary structure?

Quaternary protein structure refers to a complex formed by multiple polypeptide chains, known as subunits, which can be identical (homodimers) or different (heterodimers). In contrast, tertiary structure involves the three-dimensional folding of a single polypeptide chain. While tertiary structure is stabilized by interactions within a single polypeptide, quaternary structure is stabilized by interactions between different polypeptide chains. These interactions are primarily non-covalent, such as hydrophobic effects, but can also include covalent disulfide bridges.

What types of interactions stabilize quaternary protein structure?

Quaternary protein structure is mainly stabilized by non-covalent interactions, including hydrophobic effects, hydrogen bonds, ionic interactions, and van der Waals forces. However, covalent disulfide bridges can also play a role in stabilizing quaternary structure. These disulfide bridges form between the R groups of cysteine residues on different subunits, linking them covalently. It is important to note that the backbones of the subunits are not covalently linked, allowing for conformational changes that can affect the entire protein complex.

What is the difference between homodimers and heterodimers in quaternary structure?

In quaternary structure, homodimers consist of two identical polypeptide subunits, while heterodimers consist of two different polypeptide subunits. The term 'homo' indicates that the subunits are the same, whereas 'hetero' indicates that the subunits are different. These subunits interact to form a single protein complex, and the nature of their interactions can affect the protein's functionality and stability.

How do disulfide bridges contribute to quaternary protein structure?

Disulfide bridges contribute to quaternary protein structure by forming covalent links between the R groups of cysteine residues on different subunits. These bridges provide additional stability to the protein complex. For example, in insulin, disulfide bridges link the alpha and beta chains, stabilizing the overall structure. However, it is crucial to note that the backbones of the subunits are not covalently linked, allowing for flexibility and conformational changes within the protein complex.

Can you provide examples of proteins with quaternary structure?

Examples of proteins with quaternary structure include hemoglobin and insulin. Hemoglobin is a heterotetramer composed of four non-identical subunits, which interact primarily through non-covalent interactions. Insulin, on the other hand, consists of two subunits (alpha and beta chains) linked by disulfide bridges. These examples illustrate the diversity of quaternary structures and the different ways subunits can interact to form functional protein complexes.